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PubMed1993

Induction of bone-related proteins, osteocalcin and osteopontin, and their matrix ultrastructural localization with development of chondrocyte hypertrophy in vitro.

Endochondral bone formation occurs by a series of developmentally regulated cellular events from initial formation of cartilage tissue to stages of calcified cartilage, resorption, and replacement by bone tissue. Several studies have raised the question of the possibility that the hypertrophic chondrocytes associated with the calcifying cartilage matrix can acquire properties similar to osteoblasts. We have addressed this possibility by measuring synthesis within hypertrophic chondrocytes in vitro of two bone-related proteins, osteopontin and osteocalcin. Chondrocytes derived from chick embryo ventral vertebral tissue were cultured under conditions that promoted extracellular matrix mineralization and differentiation towards the hypertrophic phenotype as indicated by the induction of Type X collagen, alkaline phosphatase, and diminished expression of Type II collagen and the core protein of large proteoglycan. In these cultures, osteopontin synthesis was detected in early cultures in the absence of a calcified matrix; in contrast, an absence of the bone-specific protein osteocalcin was observed. However, with onset of development of the hypertrophic phenotype an induction of protein expression for osteocalcin was observed with a significant (twofold) increase in osteopontin. Maximal levels of osteocalcin synthesis occurred with the peak of alkaline phosphatase activity and Type X collagen mRNA levels. The levels of osteocalcin synthesis were induced fiftyfold from the earliest level of detection but this level was only one one-hundredth of that observed for mature chick osteoblast cultures. Osteocalcin and osteopontin were characterized by several criteria (electrophoresis, immunoblotting, chromatographic characteristics, and response to 1,25(OH)2D3) which confirmed their molecular properties as being identical to osteoblast synthesized proteins. The coordinate change in the cellular phenotype to the hypertrophic chondrocyte was shown to be concurrent with ultrastructural maturation of the cells and the accumulation of osteocalcin and osteopontin in the extracellular matrix associated with hydroxyapatite at sites of mineralization. Since the ultrastructural features of the cells in vitro and the extracellular matrix surrounding the lacunae have features of the hypertrophic chondrocyte and associated matrix in vivo, the induction of the bone-specific protein osteocalcin suggests that at least a population of these cells may develop osteoblastic phenotypic markers in association with mineralizing matrix. The detection of osteocalcin and the high level of synthesis of osteopontin may represent an advanced stage of chondrocyte hypertrophy or the possibility of a trans-differentiation of the chondrocytes to an osteoblastic-like cell.

Animals↗
PubMed1994

Alterations in cellular gene expression without changes in nuclear matrix protein content.

Cell metabolism and function are modulated in part by cell and nuclear shape. Nuclear shape is controlled by the nuclear matrix, the RNA-protein skeleton of the nucleus, and its interactions with cytoskeletal systems such as intermediate filaments and actin microfilaments. The nuclear matrix plays an important role in cell function and gene expression because active genes are bound to the nuclear matrix whereas inactive genes are not. It is unknown, however, how genes move on and off the matrix, and whether these events require compositional protein changes, i.e., alterations in protein content of the nuclear matrix, or other, more subtle alterations and/or modifications. The purpose of this investigation was to begin to determine how nuclear matrix protein composition is related to gene expression. We demonstrate that gene expression can change without apparent changes in the protein composition of the nuclear matrix in MCF10A breast epithelial cells.

Actins↗
PubMed1985

Synthesis of extracellular matrix glycoproteins by cultured microvascular endothelial cells isolated from the dermis of neonatal and adult skin.

We examined the synthesis of extracellular matrix macromolecules by human microvascular endothelial cells isolated from the dermis of neonatal (foreskin) and adult (abdominal) skin. Electron microscopy showed that both cell types produced an extracellular matrix that was strictly localized to the subendothelial space. The subendothelial matrices were initially deposited as a single discontinuous layer of filamentous, electron-dense material that progressively became multilayered. Biosynthetic studies indicated that 2-4% of the newly synthesized protein was deposited in the subendothelial matrices by both cell types. Approximately 15-20% of the radiolabeled protein was secreted into the culture medium, and the remainder was confined to the cellular compartment. Biochemical and immunochemical analyses demonstrated the extracellular secretion of type IV collagen, laminin, fibronectin, and thrombospondin by the newborn and adult cells. Whereas type IV collagen was the predominant constituent of the matrix, fibronectin was secreted into the medium, with only small amounts being deposited in the matrix. Thrombospondin was a major constituent of the matrix produced by the newborn foreskin cells but was virtually absent in the matrix elaborated by the adult cells. However, both cell types did release comparable amounts of thrombospondin into their medium. Immunoperoxidase staining for type IV collagen revealed a fibrillar network in the subendothelial matrices produced by both adult and neonatal cells. In contrast, thrombospondin, which was detected only in the matrix of newborn cells, exhibited a spotty and granular staining pattern. The results indicate that the extracellular matrices synthesized by cultured human microvascular endothelial cells isolated from anatomically distinct sites and different stages of development and age are similar in ultrastructure but differ in their macromolecular composition.

Aging↗
PubMed2004

Modulation of vascular smooth muscle cells proteoglycan synthesis by the extracellular matrix.

In this study, we investigated the effect of the extracellular matrix (ECM) secreted by vascular cells on proteoglycan (PG) synthesis by vascular smooth muscle cells in culture. PG synthesis of human aortic smooth muscle cells plated on plastic or the matrices derived from vascular endothelial cells, vascular smooth muscle cells, or THP-1 macrophages was characterized. Smooth muscle cell and macrophage matrices increased both secreted and cellular smooth muscle cells PG production by 2.5-fold to 3.9-fold, respectively, over plastic and endothelial cell matrix. Macrophage matrix was more potent than smooth muscle cell matrix in this regard. Selective enzymatic removal of chondroitin sulfates, collagen, and elastin from smooth muscle cell matrix enhanced the stimulation of PG synthesis, as did the removal of chondroitin sulfates from macrophage matrix. PG turnover rates were similar for smooth muscle cells plated on the three matrices. The newly synthesized PG from cultures plated on smooth muscle cell-, and macrophage-derived matrices had greater charge density, larger molecular size, and longer glycosaminoglycan chains than those from endothelial cell matrix cultures. These data show that the ECM plays a major role in modulating vascular smooth muscle cell PG metabolism in vitro.

Cell Division↗
PubMed1995

Control of matrix synthesis in isolated bovine chondrocytes by extracellular and intracellular pH.

The effects of extracellular and intracellular pH on matrix synthesis by isolated bovine chondrocytes were studied using radioisotope incorporation (35SO4 and 3H proline) and fluorescence techniques. Matrix synthesis exhibited a bimodal relation with decreased extracellular pH; with slight reductions (7.4 > pH > 7.1), synthesis increased (by up to 50%), whereas in more acidic media (pH < 7.1), synthesis was inhibited by up to 75% of control levels. The pHi was largely unchanged with extracellular acidity over the range producing stimulation of matrix synthesis but fell when exposed to the more acidic media shown to have an inhibitory action on matrix synthesis. The inhibition of matrix synthesis by lactic acid addition was unaffected by the lactic acid transporter alpha-CHC, suggesting H+ transport by this pathway is small. Direct imposition of a sustained intracellular acidosis (pHi = 6.65) using ammonium prepulse with amiloride inhibited matrix synthesis by about 20%. These results show that matrix synthesis by chondrocytes was affected by extracellular pH, an action which could not be entirely explained by changes to pHi.

Animals↗
PubMed2005

Decomposition and long-lasting downregulation of extracellular matrix in perineuronal nets induced by focal cerebral ischemia in rats.

The upregulation of extracellular matrix components, especially chondroitin sulfate proteoglycans, after brain injury and stroke is known to accompany the glial reaction, forming repellent scars that hinder axonal growth and the reorganization of the injured neuronal networks. The extracellular matrix associated with perineuronal nets (PNs) in the primarily injured and remote regions has not yet been systematically analyzed. We use the model of permanent middle cerebral artery occlusion (MCAO) to investigate the acute and long-lasting consequences of ischemia for PNs, related to the damage of neurons and reactions of glial cells, in spontaneously hypertensive rats. Extracellular matrix components associated with PNs around cortical interneurons and neurons in thalamic nuclei were characterized 1, 7, 14, and 35 days after MCAO, using Wisteria floribunda agglutinin (WFA) staining and immunocytochemistry. The degradation of PNs in the infarct core was initiated by loss of WFA-binding matrix components, indicating the cleavage of glycosaminoglycan chains of chondroitin sulfate proteoglycans. Immunostaining showed the subsequent removal of proteoglycan core proteins within the extending microglia/macrophage invasion zone lasting for 2 weeks after MCAO. In the cortical periinfarct region, delineated by an astrocytic scar against the infarct core, the number of WFA-stained and proteoglycan core protein-immunoreactive PNs was permanently reduced. In the homolateral ventroposterior thalamus, the delayed decrease in perineuronal matrix was related to the distribution pattern of activated microglia and massive neuronal degeneration. It can be concluded from these results that complementary to the known upregulation of matrix components in the glial scar, deficits in the expression of the neuron-associated extracellular matrix develop in the periinfarct and remote regions. These deficits may contribute to the long-lasting functional impairments after stroke.

Animals↗
PubMed1996

Repopulation of laser-perforated chondroepiphyseal matrix with xenogeneic chondrocytes. An experimental model.

Growth of chondrocytes into a xenogeneic chondroepiphyseal matrix was investigated in an in vitro experimental model by combining viable calf chondrocytes with chick epiphyseal matrix devoid of viable chondrocytes. The chondrocytes were harvested from the wrist joints of newborn calves and cultured for 2 days. The epiphyses were harvested from the distal femurs and the proximal tibias of fetal chicks after development was arrested at 17 days by freezing. The epiphyseal specimens were prepared in four ways. These included femoral and tibial epiphyses without holes and femoral and tibial epiphyses with holes made by a laser. These epiphyseal specimens were co-cultured with calf chondrocytes for various periods. After digestion of the epiphyseal matrix, viable chondrocytes were counted in suspension. Chondrocyte division in the matrix was assessed by [3H]thymidine incorporation. The growth of calf chondrocytes into the xenogeneic chick matrix was evaluated by fluorescence microscopy on fresh thick epiphyseal sections. The percentage of viable chondrocytes in the xenogeneic epiphyseal matrix increased with culture time to a maximum at day 21. The addition of laser-drilled holes was found to extend a plateau of chondrocyte viability until day 29. A decrease in cell viability was detected at later observation points. This study demonstrates that xenogeneic matrix may serve as a morphogenetic scaffold for chondrocytic growth.

Animals↗
PubMed1996

Articular chondrocyte tenascin-C production and assembly into de novo extracellular matrix.

Tenascin-C is an oligomeric glycoprotein of the extracellular matrix that is expressed in a variety of processes including development, tissue remodeling, wound healing, cell adhesion/antiadhesion, and cell/matrix interactions. Tenascin has recently been acknowledged as a component of the extracellular matrix of articular cartilage, but its function remains unclear. In this study, bovine articular chondrocytes were grown in alginate beads for 35 days to examine the kinetics of tenascin synthesis and incorporation into de novo extracellular matrix. During the culture period, 6 harvest days were established in which culture medium was recovered, alginate beads were dissociated with an EDTA solution, and chondrocytes were collected and lysed by sonication. Total DNA determination performed on the cell lysates demonstrated chondrocyte survival and proliferation. Western blotting performed on the medium, EDTA/alginate, and lysate samples demonstrated the production of both the 220 and 320 kDa tenascin size variants and their differential compartmentalization within the culture system. Tenascin was incorporated into the alginate bead matrix at a constant rate of 3.8 micrograms/day. The 320 kDa variant was produced in higher quantity, but the 220 kDa fragment was twice as likely to be incorporated into the de novo matrix. Methylene blue/acid fuchsin staining and tenascin immunohistochemistry demonstrated the incorporation of tenascin into a progressively expanding matrix surrounding the chondrocytes. The results suggest a role for tenascin in the assembly of the chondrocyte matrix and as a soluble mediator of chondrocytes with possible diverse functions for the tenascin size variants.

Animals↗
PubMed1996

Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study.

The biological basis for failure of the human anterior cruciate ligament to heal after rupture is unknown. Since this failure could be influenced by abnormalities in matrix protein production or degradation, or both, several diverse matrix protein markers were utilized to survey the state of these extracellular proteins in intrinsic anterior cruciate ligament fibroblasts. Matrix gene expression was visualized by in situ hybridization 9 to 365 days after rupture using probes for type-I collagen, collagenase, 72kDa-gelatinase, and tissue inhibitor of metalloproteinase. Remnants of anterior cruciate ligament were biopsied arthroscopically from 20 patients at reconstruction, fixed in 4% paraformaldehyde, and processed with cDNA probes for the aforementioned mRNAs. mRNA expression of type-I collagen was detected in all specimens, was equally distributed throughout the remnants, and remained evident even at 1 year after injury. Neither of the matrix-degrading enzymes nor their inhibitor (tissue inhibitor of metalloproteinase) was expressed at substantial levels at any time point. Collagen expression within the anterior cruciate ligament confirmed the viability of the ligament remnants for as long as 1 year after rupture. The lack of significant expression of the two matrix-degrading metalloproteinases by the fibroblasts is not consistent with an autodegradation of the remaining ruptured ligament tissue, and whether the lack of matrix remodelling may account, at least in part, for the poor healing response of the anterior cruciate ligament remains to be determined. This initial investigation by in situ hybridization techniques provides a descriptive profile of matrix gene expression in the damaged human anterior cruciate ligament.

Adolescent↗
PubMed1999

Effect of demineralized bone matrix on polymorphonuclear leukocyte degranulation.

The potential use of allogenic demineralized bone matrix to augment or treat bone defects or nonunions in animals and humans is currently being investigated. Demineralized bone matrix induces osteogenesis by a multistep cascade of endochondral ossification that is mediated by bone-induction factors. The migration and activation of polymorphonuclear leukocytes appear to be critical in the initiation of the cascade of osteogenesis induced by demineralized bone matrix. This study examined the effects of demineralized bone matrix on the degranulation of polymorphonuclear leukocytes. Demineralized bone matrix stimulated the release of polymorphonuclear leukocyte-specific, but not azurophilic, granules in a time and dose-dependent manner. The ability of the bone matrix to induce this degranulation was independent of its size and species. The mechanism by which this degranulation occurs is not completely understood; however, it is known that it does not occur by means of a receptor that requires guanidine triphosphate-dependent regulatory proteins as does polymorphonuclear-leukocyte degranulation induced by N-formyl peptide. The factor that stimulates degranulation is not type-I collagen but rather appears to be a cytokine that has a heparin-binding domain and a molar mass of 10-70 kDa. Loss of the ability of demineralized bone matrix to induce degranulation of polymorphonuclear leukocytes correlated positively with the loss of its ability to induce bone formation.

Animals↗
PubMed2006

Development of a model bladder extracellular matrix combining disulfide cross-linked hyaluronan with decellularized bladder tissue.

[Image: see text] In this work we investigate the feasibility of modifying porcine-derived BAM to include HA with a view to developing a model, artificial extracellular matrix for the study of bladder cell-matrix interactions. HA-DPTH was incorporated into BAM disks and then cross-linked oxidatively to a disulfide containing hydrogel. Disks were seeded with bladder smooth muscle cells (BSMC) and UEC under three culture configurations and incubated for 3, 7, and 14 d. At each time point, matrix contraction was measured, and media supernatants assayed for cell-secreted gelatinase activity. To evaluate cell adherence and organization, triple immunofluorescent labeling of cell nuclei, actin cytoskeleton, and focal contacts was performed. HA-modified BAM exhibited a significant increase in matrix contraction and induced a higher level of cell-secreted gelatinase activity compared to unmodified BAM. Immunofluorescent labeling demonstrated that BSMCs remained adherent to both scaffold types over time. The distribution and organization of the cytoskeleton and focal contacts did not appear to be altered by the presence of HA. Interestingly, cellular infiltration into modified BAM was evident by 7 d and continued beyond 14 d, while BSMCs seeded onto unmodified BAM remained localized to the surface out to 14 d, with minimal infiltration evident only at day 28. These differences in cell infiltration support the gelatinase activity results. Increases in cell migration and matrix proteolysis in the presence of HA may be contributing factors toward BAM remodeling leading to increased matrix contraction with time. The model ECM developed in this work will be utilized for future studies aimed at elucidating the mechanisms controlling key remodeling events associated with bladder repair. Matrix contraction of cell-seeded BAM scaffolds.

Animals↗
PubMed1995

Oxidation of mesangial matrix using a mixed function oxidase system augments adhesion of macrophages: possible role of macrophage scavenger receptors.

Oxygen radicals are believed to play a role in the pathogenesis of aging and glomerular injury. Changes in cellular function may result from modification of the extracellular matrix with which they interact. We produced oxidized mesangial matrix protein using a mixed function oxidase system. Carbonyl content of the oxidized matrix was significantly increased. Adhesion of macrophages to the oxidized mesangial matrix was significantly enhanced, an effect which was significantly abrogated by scavenger receptor blockade with polyinosinic acid or dextran sulfate. Neither polyinosinic acid nor dextran sulfate diminished macrophage adhesion to unmodified matrix. These data demonstrate for the first time that mesangial matrix can undergo oxidation and that such oxidation may promote accumulation of macrophages in the mesangium via interaction of macrophage scavenger receptors with oxidized matrix proteins.

Analysis of Variance↗
PubMed1996

Deposition of collagen VI in the extracellular matrix during mouse embryogenesis correlates with expression of the alpha 3(VI) subunit gene.

Collagen VI is a microfibrillar component of the extracellular matrix that is predicted to have an important structural role in matrix organization and a biological function in mediating cell-matrix interactions. Secreted collagen VI molecules are composed of three distinct subunits, the alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains. To determine when, and in which tissues, collagen VI is likely to have a role in embryonic processes, we have analyzed the expression patterns of the three subunit chains during postimplantation mouse development by reverse transcriptase-PCR (RT-PCR), in situ hybridization, and immunofluorescence. No collagen VI protein could be detected in the mouse embryo until Day 11.5 of gestation, when low levels were localized within the mesoderm layer of the visceral yolk sac, the subepidermal matrix of branchial arches, and the vessel wall of the dorsal aorta. Levels of collagen VI mRNA and protein increased during the period from Days 12.5 to 14.5 in the visceral yolk sac, subepidermal mesenchyme, lung, gut, meninges, muscle, perichondrium, and vertebral column. The cartilage matrix of ribs and developing long bones was not stained with collagen VI antisera, but pericellular staining of chondrocytes was seen in both tissues. Low levels of collagen VI mRNA and protein were seen in the fetal liver except for the connective tissue of the liver capsule, which was highly stained. Collagen VI was first detected at significant levels in the developing heart on Day 14.5. These data demonstrate a tissue-specific onset of collagen VI synthesis and deposition in the extracellular matrix of developing mouse embryos at a much later stage of development than that reported for fibronectin or collagen I. Sensitive RT-PCR assays showed that alpha 1(VI) and alpha 2(VI) mRNAs were amplified from extracts of embryonic tissues as early as Day 7.5, while alpha 3(VI) mRNA was not detected until Day 10.5. Expression of the alpha 3(VI) gene immediately preceded the appearance of collagen VI protein in embryonic tissues. This correlation is consistent with the proposal that expression of alpha 3(VI) chains regulates the formation and secretion of collagen VI trimers and collagen VI matrix deposition during development.

Animals↗
PubMed1998

Laminin-1 and the RKRLQVQLSIRT laminin-1 alpha1 globular domain peptide stimulate matrix metalloproteinase secretion by PC12 cells.

Here we have investigated the ability of laminin-1 and specific laminin-1-derived synthetic peptides to stimulate neuronal cell matrix metalloproteinase secretion. Zymographic analysis of conditioned media from laminin-1-treated PC12 and NG108-15 cells revealed a 72-kDa matrix metalloproteinase which was not secreted by untreated cells. Laminin-1 alpha1 chain-derived synthetic peptides, AASIKVAVSADR (LAM-L) and RKRLQVQLSIRT (AG-73), also stimulated PC12 cell secretion of a 72-kDa matrix metalloproteinase. We further investigated the structural requirements of AG-73 for cell attachment, neurite outgrowth, and matrix metalloproteinase secretion using a series of AG-73 analogs that had single amino acids substituted with alanine. At the substrate levels tested, the AG-73 peptide promoted the adhesion of 67% of the PC12 cells and neurite outgrowth in 71% of the PC12 cells. Substitutions in any one of the amino acids within the central LQVQ sequence resulted in a large reduction in cell attachment whereas substitution in the carboxyl terminal proximal amino acids L, S, and R had little effect on attachment. Alanine substitution of any of the amino terminal proximal LQV amino acids and the carboxyl terminal L, I, and R residues resulted in a 65-91% reduction in neurite outgrowth. These data demonstrate that the sequence requirements for cell attachment and neurite outgrowth were not necessarily coupled but that the sequence requirements for neurite outgrowth and matrix metalloproteinase secretion were identical. We conclude that laminin-1 is able to stimulate neuronal cells to secrete a matrix metalloproteinase. Further, this study identifies the LQVXLXIR laminin-1 alpha1 globular domain peptide to be capable of stimulating both neurite outgrowth and matrix metalloproteinase secretion.

Animals↗
PubMed1996

Spatial and temporal variations in extracellular matrix of periocular and corneal regions during corneal stromal development.

The development of the avian corneal stroma occurs in discrete developmental stages. During this sequence of events, the neural crest-derived corneal fibroblast precursor cells are surrounded by distinct extracellular matrices which change both spatially and temporally. To elucidate the role of these matrices, extracellular matrix components in the periocular mesenchyme and cornea were analysed prior to and during migration and differentiation of corneal fibroblasts using antibodies against collagens, proteoglycans and glycoproteins. Previous work has concentrated on the matrix of the corneal stroma rather than the matrix of the periocular mesenchyme. Since the precursors of the corneal fibroblasts are present within the must migrate through the periocular mesenchyme prior to entry into the cornea proper, this environment was fully evaluated. The present study documents the matrix composition of both the cornea and periocular mesenchyme at developmental stages that are prior to and after initiation of corneal invasion by the corneal fibroblast precursors. Variations in matrix molecules comprising both the periocular mesenchyme and cornea were demonstrated. These include changes in the distribution of collagen types I, II, III, IV and VI; the proteoglycans decorin and lumican; as well as the adhesive glycoproteins tenascin, fibronectin and laminin. It is hypothesized that the variations in matrix localization are important in the regulation of cell migration and differentiation during normal corneal development. Any regulation is likely to involve a combination of components found in the extracellular matrices and therefore, a consideration of the matrix rather than isolated components is required.

Animals↗
PubMed2002

Extracellular matrix oxidation modulates survival, NF-kappaB translocation, and MAPK activity in mesangial cells.

Inflammatory injury to the kidney may oxidize extracellular matrix proteins. These changes appear to impair adhesion of glomerular mesangial cells and might impact signaling mechanisms in these cells. In this study we evaluated how extracellular matrix oxidation could modulate the development of apoptosis as well as the activity of the transcription factor NF-kappaB and that of the MAPK family members ERK-1,2 and JNK. Exposure of mesangial cells to oxidized matrix enhanced the percentage of apoptotic cells. Western blot analysis revealed diminished levels of the phosphorylated form of ERK-1,2 in cells on oxidized matrix, while levels of phosphorylated JNK were increased. Cells on unmodified matrix were found to have rapid translocation of the p65 subunit of NF-kappaB, which was attenuated in cells on oxidized matrix. These findings suggest that extracellular matrix oxidation may impair survival of mesangial cells in association with decreased levels of pERK-1,2, increased levels of pJNK, and diminished nuclear translocation of the transcription factor NF-kappaB.

Active Transport, Cell Nucleus↗
PubMed1993

Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy.

Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capillaries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra- and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focus on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucose-induced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of extracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level.

Animals↗
PubMed1988

Structure of the cumulus matrix and zona pellucida in the golden hamster: a new view of sperm interaction with oocyte-associated extracellular matrices.

Hamster oocyte-cumulus complexes (OCC), with and without sperm, were structurally analyzed by light- and electron microscopy using freeze substitution. This method has yielded a clear picture of the extracellular oocyte investments, the cumulus cell matrix and the zona pellucida. The cumulus matrix has an overall homogeneous fibrillar structure which appears to attach to cumulus cells at their filopodial extensions. The matrix also extends into the outer regions of the zona pellucida. The zona pellucida has a distinct porous configuration throughout its entire structure. During gamete interaction experiments, capacitated hamster sperm with ultrastructurally intact acrosomes were found throughout the matrix. Sperm had dramatic effects on the matrix, resulting in compression and stretching. Sperm found on the zona pellucida had initiated or completed the acrosome reaction. During the initial stages of the acrosome reaction, the matrix was in contact with the sperm. At later stages of the acrosome reaction, there was a complete loss of matrix material in regions near the sperm.

Animals↗