Search PubMed⌕ Search

Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV.

Excessive mesangial cell (MC) proliferation is a hallmark of many glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P. Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401-410) we found that inhibition of isozyme cyclic-3',5'-nucleotide phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by activating cAMP-dependent protein kinase (PKA) and by decreasing activity of mitogen-activated protein kinase (MAPK). We also found that inhibition of another PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini, C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney Int. 46:28-36). We thus explored whether administration in vivo of the selective PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV antagonist, rolipram (RP), can attenuate development of mesangioproliferative glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS). Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did not develop proteinuria and maintained normal renal function when examined 5 d after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN-rats the morphology of glomeruli showed a reduction in cellularity compared with control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta -65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a significant reduction of alpha-smooth muscle actin expression by activated MC; in contrast, immunostaining for platelet antigens and laminin were not different. The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats. We conclude that antagonists of PDE-III and PDE-IV administered in submicromolar concentrations in vivo to ATS-injected rats can decrease the activation and proliferation of MC, inhibit the macrophage accumulation, and prevent proteinuria in the acute phase of MSGN. We propose that PDE isozyme inhibitors act to block (negative "crosstalk") the mitogen-stimulated intracellular signaling pathway which controls MC proliferation due to activating of the cAMP-PKA pathway. These results suggest that antagonists of PDE-111 and IV may have a suppressive effect in acute phases or relapses of glomerulopathies associated with MC proliferations.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

The cytoskeletal linking proteins, moesin and radixin, are upregulated by platelet-derived growth factor, but not basic fibroblast growth factor in experimental mesangial proliferative glomerulonephritis.

The expression of the two cytoskeletal linking proteins, moesin and radixin, was examined in experimental mesangial proliferative nephritis in rats (anti-Thy1 model). Moesin and radixin mRNA and protein are constitutively expressed in all cell types of normal rat glomeruli, except podocytes. In the anti-Thy1 model the expression of moesin and radixin was increased in infiltrating macrophages and in activated, alpha-smooth muscle actin-positive mesangial cells and was concentrated in the cellular extensions of mesangial cells in areas of glomerular remodelling. Studies using neutralizing antibodies demonstrated that the increase in moesin and radixin expression by mesangial cells is mediated by PDGF, but not bFGF. The increase in these cytoskeletal proteins appears to be regulated primarily (radixin) or partially (moesin) posttranscriptionally. The data suggest that PDGF mediated upregulation of the cytoskeletal proteins, moesin and radixin, is important for cell migration and other changes that accompany the coordinated restoration of glomerular architecture after injury.

Actins↗
PubMed1996

Infusion of ovine C5a into sheep mimics the inflammatory response of hemodialysis.

Previous studies in our group have explored the inflammatory response in sheep to dialysis with a variety of different hemodialysis membranes. In the present study we investigated the potential role of C5a in mediating inflammatory responses that have been attributed to complement activation in the extracorporeal setting. Sheep C5a was infused into sheep in a manner that simulated exposure to this anaphylatoxin during dialysis. C5a infusion into sheep was shown to produce a dose-dependent neutropenia that was quantitatively and temporally identical to the response of sheep undergoing dialysis with complement-activating membranes. The two lowest doses used (0.25 and 0.50 micrograms/kg), which resulted in concentrations below the detectable limits of current assays (10 ng/ml), produced significant neutropenia (21.8% and 78.1%, respectively). The ability of the neutrophils (PMNs) to bind fluorescein isothiocyanate-C5a or initiate a respiratory burst in response to phorbol myristate acetate were also affected in a dose-dependent manner. In contrast, C5a alone was not able to produce significant release of lactoferrin, a specific granule constituent, suggesting that degranulation of PMN-specific and primary granules requires secondary stimuli. The production of thromboxane A2 and thromboxane's consequent cardiopulmonary effect of increasing mean pulmonary artery pressure were both observed in a dose-dependent fashion. However, larger amounts of C5a were required to elicit these latter responses as compared with the PMN activities. These results suggest that C5a may be a primary mediator of complement-dependent events that occur during extracorporeal therapies such as hemodialysis, and they also suggest that very little complement activation is necessary to activate leukocytes, whereas higher thresholds are required to produce cardiopulmonary responses.

Amino Acid Sequence↗
PubMed1996

Identification of a lipopolysaccharide inducible transcription factor in murine macrophages.

To study macrophage genes activated by lipopolysaccharide (LPS) we have constructed a cDNA library using the mouse macrophage cell line, RAW 264.7. By differential screening, a gene, designated LRG-21, was identified that showed nucleic acid sequence homology to rat liver regenerating factor-1 (LRF-1) and human activating transcription factor-3 (ATF3). Both LRG-21 and LRF-1 are transcribed within an hour following stimulation and in the absence of protein synthesis. The predicted protein sequence of LRG-21 consists of 181 amino acids with a molecular weight of 20.7 kDa. All three sequences contain basic and leucine zipper regions characteristic of the c-Fos and c-Jun family of transcription factors, but the remainder of the sequences are unrelated to this family. Recombinant LRG-21 has been shown to bind to a phorbol ester promoter element. Additional experiments have shown that LRG-21 is also induced by interferon-gamma (IFN-gamma) and by interleukin-4 (IL-4) in both RAW264.7 cells and murine peritoneal macrophages. Based on these observations, it is likely that LRG-21 plays an important role in macrophage activation.

Activating Transcription Factor 3↗
PubMed1996

Differential expression of transforming growth factor-beta isoforms and receptors in experimental membranous nephropathy.

In membranous nephropathy (MN) overproduction of matrix by glomerular epithelial cells (GEC) is believed to be responsible for glomerular basement membrane thickening and spikes. We studied experimental MN in rats (passive Heymann nephritis, PHN) at 5, 10 and 30 days. PHN rats exhibited a marked increase in GEC immunostaining for TGF-beta 2 at all time points. TGF-beta 3 staining was increased at day 10 only, and TGF-beta 1 was unchanged. Glomerular mRNA for TGF-beta 2 and -beta 3 was increased by day 5 when urine protein increased, whereas TGF-beta 1 was not. TGF-beta 2 bioactivity was increased at day 5. There was also a marked increase in GEC immunostaining for TGF-beta receptor type I (T beta IR) and TGF-beta receptor type II (T beta IIR) at all time points in PHN. mRNA levels for both receptors increased at day 5. Increases in protein expression and mRNA levels for the TGF-beta 2 and -beta 3 isoforms, and T beta IR and T beta RII were prevented by complement depletion. We conclude that complement-mediated injury to the GEC in vivo is associated with the up-regulation of TGF-beta 2 and -beta 3 isoforms, an increase in TGF-beta 2 bioactivity, and an increase in T beta RI and T beta RII expression. This contrasts with changes in TGF-beta 1 reported in mesangial disease, suggesting that TGF-beta 2 and -beta 3 may be important in diseases of the GEC. The differential expression of TGF-beta isoforms and receptors may be important determinants of the GEC response to injury.

Animals↗
PubMed1996

Transfected CD59 protects mesangial cells from injury induced by antibody and complement.

CD59 is a complement regulatory protein on the glomerular cells that inhibits C5b-9 assembly and insertion. We employed an overexpression strategy to determine the functional significance of CD59 in mesangial cells. We made a CD59 expression vector tagged with FLAG utilizing site-directed mutagenesis and PCR, which allows transfected CD59 to be distinguished from the constitutively expressed protein. In stable clones, overexpressed CD59 was clearly detected immunocytochemically both by anti-FLAG and anti-CD59 antibody in a granular pattern. The overexpression of CD59 was also confirmed by Western blotting. To determine if overexpression of CD59 by mesangial cells protected these cells from C5b-9 attack, we performed complement-mediated cell lysis assays. CD59-transfected mesangial cells demonstrated marked resistance to complement-mediated cell lysis which was reversed in the presence of antibody to CD59. We also investigated the role of CD59 in protecting cells from the effects of membrane insertion of sublytic quantities of C5b-9. Overexpressed CD59 suppressed production of superoxide, one of the inflammatory mediators induced by sublytic C5b-9 attack. These results demonstrate directly that transfected CD59 functions as a potent protector of mesangial cells against both lytic and sublytic attack by C5b-9. CD59 may be an important regulator of complement-mediated disease in the glomerular mesangium.

Animals↗
PubMed1996

Changes in cell-cycle protein expression during experimental mesangial proliferative glomerulonephritis.

A characteristic response to mesangial cell injury is proliferation, which is closely linked to mesangial matrix accumulation and the progression of glomerular disease. Cell proliferation in non-renal cells in vitro is regulated at the level of the cell-cycle by specific cyclins and their catalytic partners, cyclin dependent kinases (CDK). Cyclin kinase inhibitors (CKI) prevent proliferation by inhibiting cell-cycle progression. However, the expression of cell-cycle regulatory proteins in the kidney and in renal disease is unknown. To determine this we studied the expression of cell-cycle proteins in vivo in normal rats and rats with experimental mesangial proliferative glomerulonephritis (Thy1 model). Normal quiescent rat glomeruli have a differential expression for CKI's, where p27Kip1 is highly expressed, and the levels for p21 (Cip1, Waf1, Sdi1, Cap20) (p21) are low. The onset of mesangial cell proliferation in Thy1 glomerulonephritis is associated with a reduction in p27Kip1 levels when mesangial cell proliferation is maximal. Mesangial cell proliferation in vivo is also associated with an increase in glomerular expression of cyclin A, and an increase in expression and activity for CDK2. The resolution of mesangial cell proliferation was associated with a return to baseline levels for p27Kip1, while the expression for p21 increased substantially. Furthermore, mesangial cell p21 expression was maintained following the resolution of proliferation. These results provide evidence for a complex interplay of cell-cycle regulatory proteins during the glomerular response to injury in vivo. The marked increase in CDK2 expression during mesangial cell proliferation and the sustained increase in p21 expression following the resolution of mesangial cell proliferation suggests that the in vivo expression of certain cell-cycle proteins may differ from that described in non-renal cells in vitro.

Animals↗
PubMed1996

Role of the complement membrane attack complex (C5b-9) in mediating experimental mesangioproliferative glomerulonephritis.

Previous studies have demonstrated that most pathologic changes in the antithymocyte serum (ATS) model of mesangioproliferative glomerulonephritis are complement-dependent. These include mesangiolysis, glomerular platelet infiltration, mesangial cell proliferation, mesangial cell production of growth factors and phenotypic change to express alpha-actin, glomerular macrophage infiltrate, mesangial matrix expansion, and proteinuria. The mechanism by which complement mediates these effects has not been defined. Because neutrophils do not participate in the ATS model, we hypothesized that the complement effects observed are consequent to glomerular cell insertion of the C5b-9 membrane attack complex of complement. This hypothesis was tested utilizing PVG rats which exhibit an absence of C6 inherited in an autosomal recessive pattern. C6 deficient (C-) PVG rat serum activated by zymosan produced normal amounts of C5a compared to normocomplementemic (C+) PVG rat controls but no C5b-9. When ATS was induced, C- PVG rats had a significant and marked reduction in mesangiolysis, platelet infiltration, mesangial cell proliferation, alpha-actin expression, macrophage infiltration, collagen IV deposition, and proteinuria compared to C+ controls. The reduction in each of these parameters was comparable to that achieved by systemic complement depletion of C+ PVG rats with cobra venom factor. These findings establish the role of C5b-9 in mediating each of the complement-dependent features of the ATS model and indicate that C5b-9 accounts for all of the complement-mediated effects observed. This study provides the first documentation of a functional role for C5b-9 in mediating a non-membranous inflammatory type of glomerular injury in vivo.

Animals↗
PubMed1996

SPARC is expressed in renal interstitial fibrosis and in renal vascular injury.

Tubulointerstitial inflammation and fibrosis are critical determinants for renal function and prognosis in a variety of human nephropathies. Yet, the pathophysiology of the injury remains obscure. We investigated the expression of SPARC (secreted protein acidic and rich in cysteine) by immunohistochemistry and in situ hybridization in experimental models characterized by tubulointerstitial fibrosis and matrix expansion in rats. SPARC is a secreted glycoprotein that has been demonstrated to affect cellular interaction with matrix proteins, modulate cell proliferation, bind to and/or inhibit growth factors such as PDGF and bFGF, and regulate angiogenesis. Interstitial expression of SPARC was most prominent in passive Heyman nephritis (PHN), chronic cyclosporine A (CsA) nephropathy, and the remnant kidney model and, to a lesser extent, in angiotensin II (Ang II)-infused animals. SPARC protein and mRNA were substantially increased at sites of tubulointerstitial fibrosis/matrix expansion. In the PHN model, SPARC protein was expressed by interstitial fibroblasts that also produced alpha-smooth muscle actin ("myofibroblasts") and correlated both temporally (r = 0.97) and spatially with sites of type I collagen deposition. Interstitial cell proliferation preceded the development of interstitial fibrosis, and maximal SPARC expression (d15) coincided with the initial decline in interstitial proliferation. In the Ang II-infusion model, which is characterized by arteriolopathy and tubulointerstitial injury, an increase in SPARC protein and mRNA was also seen in injured blood vessels. SPARC was shown to be expressed by vascular smooth muscle cells and also by cells in the adventitia of hypertrophied arteries. In summary, SPARC was transiently expressed by interstitial fibroblasts at sites of tubulointerstitial injury and fibrosis, and by smooth muscle cells and cells in the adventitia of injured arteries in the Ang II-model. In addition to its proposed role in extracellular matrix deposition. the antiproliferative properties of SPARC might contribute to the resolution of interstitial fibroblast proliferation in the PHN model.

Actins↗
PubMed1996

Beneficial effects of systemic immunoglobulin in experimental membranous nephropathy.

To test the hypothesis that systemic administration of immunoglobulin might reduce glomerular injury in membranous nephropathy through mechanisms involving inhibition of complement activation, we studied the passive Heymann nephritis (PHN) model of membranous nephropathy in rats. The daily administration of immunoglobulin goat IgG (600 mg/kg i.p.) reduced proteinuria by 52%. Quantitative immunohistochemical analysis showed that the glomerular deposition of C3c, an indicator of ongoing complement attack, and of C5b-9 was significantly decreased in the immunoglobulin treated group, while deposition of anti-Fx1A was not affected. Electron microscopic analysis demonstrated that the extent of subepithelial immune complexes did not appreciably differ between treated and control animals. Systemic complement levels were not altered by immunoglobulin treatment. These data suggest that the reduction in proteinuria that resulted from systemic immunoglobulin administration was mediated by modifying the effect of complement induced glomerular injury. This interpretation was further supported by in vitro data that documented a significant reduction in C5b-9 induced glomerular epithelial cell lysis in the presence of both goat and rat IgG. These results indicate that systemic administration of immunoglobulin can substantially reduce ongoing complement activation in the glomerulus in PHN rats and that this effect is associated with a significant reduction in glomerular injury.

Animals↗
PubMed1996

Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats.

The 5/6 nephrectomy model is used to study pathogenetic mechanisms underlying chronic renal failure. We previously demonstrated that increased mesangial cell proliferation and glomerular PDGF B-chain expression precede glomerulosclerosis in this model. In the present study we have assessed the concomitant changes in the cortical tubulointerstitium. A wave of tubular and interstitial cell proliferation (as determined by immunostaining for PCNA) occurred at week 1 after 5/6 nephrectomy. This wave preceded the peak glomerular cell proliferation by one week. Tubulointerstitial cell proliferation decreased thereafter and reached control values by week 10. In situ hybridization and immunostaining for PDGF B-chain and beta-receptor in sham-operated controls showed labeling of distal tubules and collecting ducts, while no signal was present in the interstitium. PDGF B-chain mRNA and protein expression was markedly increased in tubules at weeks 2 and 4 after 5/6 nephrectomy and in the interstitium (particularly in areas of inflammatory infiltrates) at weeks 2 to 10. Similar changes occurred with PDGF receptor beta-subunit immunostaining. Interstitial expression of desmin and alpha-smooth muscle actin (markers of myofibroblasts) progressively increased after week 1. Interstitial influx of monocytes/macrophages with focal accentuation started at week 2. Counts of lymphocytes, neutrophils and platelets showed only minor changes. In parallel to the monocyte/macrophage influx, progressive interstitial accumulation of collagens I and IV, laminin, and fibronectin occurred. All of these changes were correlated with the increase in serum creatinine, proteinuria and an index of tubulointerstitial damage. We conclude that tubulointerstitial changes after 5/6 nephrectomy show similarities with those observed in the glomeruli. Tubular and interstitial overexpression of PDGF B-chain and its receptor may play a role in mediating fibroblast migration and/or proliferation in areas of tubulointerstitial injury.

Actins↗
PubMed1996

Mobilization of Philadelphia-negative peripheral blood mononuclear cells in chronic myeloid leukaemia using hydroxyurea and G-CSF (filgrastim).

A relatively simple and non-toxic out-patient-based regimen for the mobilization of Philadelphia-negative (Ph-ve) mononuclear cells in chronic myeloid leukaemia (CML) was evaluated in 10 patients, nine in stable chronic phase and one in accelerated phase. They received oral hydroxyurea at a mean dose of 3.5 g/m2 daily for 7 d, followed by 300 micrograms of G-CSF daily until the last day of harvesting. In the nine chronic-phase patients the mean number of days from the end of hydroxyurea to the commencement of harvesting was 14.5 (range 10-18). The patient in accelerated phase recovered and was harvested after 6 d. The mean number of aphereses performed was 3.4. Adequate numbers of stem cells were obtained in 9/10 patients judged by our usual criteria. Side-effects were mild in comparison to published intravenous schedules. No patients lost their hair. Five (50%) patients required admission with neutropenic fever which responded to antibiotics in all cases. Four (40%) patients developed a transient rash and four (40%) experienced mild oral mucostis. This level of toxicity enabled half of the patients to be treated entirely on an out-patient basis. The harvest products were analysed for cells belonging to the leukaemic clone by conventional cytogenetics, FISH and PCR. All were PCR positive. The mean Ph positivities by cytogenetics and FISH were comparable at 18.1% and 15% respectively. Half the patients had > 98% normal metaphases. We conclude that this approach is comparable in efficacy to published intravenous regimens and significantly less toxic. It can be safely used at diagnosis before interferon therapy commences.

Administration, Oral↗
PubMed1996

In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci.

The in vitro activities of LY333328 were compared with those of vancomycin, teicoplanin, and quinupristin-dalfopristin (Synercid) against 219 strains of enterococci and staphylococci, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MICs and MBCs were determined by a microtiter dilution protocol. LY333328 demonstrated superior activity against vancomycin-resistant enterococci and was the only antibiotic which was bactericidal. Its potency was comparable or superior to those of other antibiotics tested against methicillin-resistant staphylococci.

Anti-Bacterial Agents↗
PubMed1996

Assessment of IgH PCR strategies in multiple myeloma.

AIMS: To compare the ability of four commonly used PCR techniques to demonstrate clonal IgH rearrangements in multiple myeloma. METHODS: Bone marrow samples (containing a minimum of 10% plasma cells) were obtained from 127 patients with confirmed multiple myeloma. Framework 3 (Fr3) PCR was performed in all cases and the Framework 1 (Fr1f) PCR, which utilises six VH family specific primers, in 98 cases. In addition, 44 cases were assessed by Fr3, Fr1f, Framework 2 (Fr2) and Framework 1 consensus (Fr1 con) PCR techniques. JH primer selection was also assessed such that each PCR strategy was performed twice in each of the 44 cases, using the JH consensus primer (JH con) alone and then repeated with an equimolar mixture of JH con, JH3 and JH6 (JH mix). RESULTS: Clonal rearrangements were demonstrated in 71 (56%) of 127 cases with the Fr3 PCR and in 52 (53%) of 98 with the Fr1f PCR. However, by using both techniques it was possible to demonstrate clonal IgH rearrangements in 92 (75%) of 122 cases. Forty four cases were assessed by all four PCR techniques; in these cases the Fr3 and Fr1f PCRs demonstrated clonal rearrangements in 26 (59%) cases with a combined yield of 34 (77%). The Fr2 and Fr1 con PCR techniques had inferior pick up rates, demonstrating clonal rearrangements in 21 (48%) of 44 cases and a combined yield of 28 (63%). The Fr2 PCR did, however, demonstrate a clonal rearrangement in one case negative by both Fr3 and Fr1f. Two additional rearrangements were demonstrated by using JH mix; one became positive by Fr3, Fr1f and Fr2 and the other positive by Fr1f, Fr1 con and Fr2. CONCLUSIONS: By utilising both the Fr3 and Fr1f PCR techniques it is possible to demonstrate definitive clonal rearrangements in the majority of patients with multiple myeloma. The Fr1 con and Fr2 PCR techniques have inferior pick up rates but may detect some additional rearrangements.

Bone Marrow Examination↗
PubMed1996

Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection.

Aims-To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection.Methods-PBPC collections from 29 patients with MM were analysed for the presence of clonal immunoglobulin heavy chain (IgH) gene rearrangements with a fluorescence based PCR technique. In addition, the PBPC from eight of the 29 patients were "purged" by selection of CD34 positive haematopoietic progenitors with an avidin-biotin immunoabsorption column (Ceprate). In each case the unmanipulated PBPC, CD34 positive and waste fractions were all assessed for the presence of clonal IgH rearrangements.Results-Clonal IgH rearrangements (identical with those demonstrated in diagnostic bone marrow samples) were demonstrated in 10 (35%) of 29 cases and seemed to be confined to those with significant residual bone marrow disease. Clonal rearrangements were evident in the PBPC of two of the eight patients who underwent CD34 selection; in both instances a "clonal purge" was seen as it was not possible to demonstrate the clonal rearrangement in the CD34 positive fraction. In four of the six remaining cases the normal polyclonal fingerprint could not be demonstrated in the CD34 positive fraction, which is consistent with a significant reduction in contaminating B cells.Conclusions-Clonal cells contaminate PBPC collections in a significant proportion of patients with MM and may be eliminated by CD34 positive selection.

Journal Article↗
PubMed1996

Role of cytokines and growth factors in glomerulonephritis: a chance for future therapeutic intervention.

Recent studies using experimental models of glomerular disease have not only elucidated the pathophysiologic basis of glomerular disease, but have also identified potential new treatments. In this review, we will provide examples of how cytokines and cytokine antagonists may be used in the future treatment of glomerular disease. Treatments will be presented for each of the pathophysiologic phases of disease, beginning with the etiology, the development of a nephritogenic immune response, the mechanisms by which glomerular injury occurs, the response of the glomerulus to injury that results in cell proliferation and matrix expansion, and the factors that lead to healing or scarring. Special emphasis is placed on the cytokines interleukin 1 beta and tumor necrosis factor alpha, which are proinflammatory cytokines that potentiate neutrophil- and monocyte-mediated glomerular injury, and on the growth factors platelet-derived growth factor and transforming growth factor beta, which are involved in cell proliferation and matrix expansion that occur as glomerular cells respond to injury. The identification of the specific mediators involved in glomerular disease should provide new therapies that are more specific and less toxic than current conventional immunosuppressive regimens.

Animals↗