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Gunter Wolf

Publications and source records attributed to Gunter Wolf.

At least 55 records · Page 3Linked to original sources
PubMed2004

Albumin up-regulates the type II transforming growth factor-beta receptor in cultured proximal tubular cells.

BACKGROUND: Clinical and experimental observations suggest that proteinuria is not merely a marker of chronic nephropathies, but may also be involved in the progression to end-stage renal failure. Filtered proteins are taken up by tubular cells, and overwhelming this system may lead to tubular synthesis of various proinflammatory and profibrogenic cytokines, including transforming growth factor-beta (TGF-beta). TGF-beta acts by first binding to specific receptors. We studied in an in vitro system using a well-defined mouse proximal tubular cell line (MCT cells) whether fatty acid-free bovine albumin modulates expression of specific receptors for TGF-beta. METHODS: MCT (and LLC-PK1) cells were challenged in serum-free medium with different concentrations of albumin. Activation of a local renin-angiotensin system was tested by real-time polymerase chain reaction (PCR) for renin and angiotensinogen transcripts and determination of secreted angiotensin II (Ang II) by enzyme-linked immunosorbent assay (ELISA). Some cells were also treated with the AT1 receptor antagonist losartan. TGF-beta receptor types I and II mRNA levels were determined by Northern analysis whereas protein abundance was measured by Western blots. To test for a functional consequence of up-regulated TGF-beta receptors, MCT cells were preincubated with albumin and subsequently treated with low-dose TGF-beta that normally does not induce collagen type IV expression by itself. Downstream signaling events were detected by Western blots for phosphorylated Smad2. Scatchard assays with [125I]TGF-beta1 were performed to estimate affinity and number of specific binding sites. Different length TGF-beta type II promoter constructs linked to CAT reporter were transiently transected into MCT cells to determine transcriptional activity. RESULTS: Incubation of MCT cells with 0.5 to 10 mg/mL albumin leads to an increase in type II TGF-beta receptor mRNA and protein expression without influencing type I receptors. An increase in type II TGF-beta receptor protein expression was detected after 12 hours of albumin incubation and was still detectable after 48 hours. The albumin-mediated increase in type II TGF-beta receptor mRNA was attenuated in the presence of 1 micromol/L losartan, suggesting involvement of a local renin-angiotensin system. MCT cells treated with albumin significantly increased expression of angiotensinogen and renin transcripts and also secreted more Ang II into the culture supernatant. Analysis of transcriptional activity showed that promoter segments containing activating protein (AP-1)-binding sites are necessary for albumin-induced transcription of the TGF-beta type II receptor. Binding assays revealed that albumin treatment significantly increased the overall binding sites as well as the affinity for TGF-beta. This effect had functional consequences because MCT cells pretreated with albumin reacted with a stronger TGF-beta-mediated phosphorylation of down-stream Smad2 and also increased collagen IV expression compared with control cells. CONCLUSION: Our findings indicate that albumin up-regulates ligand-binding TGF-beta receptors on cultured proximal tubular cells. Albumin-induced activation of local Ang II production appears to be responsible for this effect. This may amplify the matrix-stimulatory actions of TGF-beta on tubular cells and could be a novel mechanism for how proteinuria exhibits pathophysiologic effects on tubular cells ultimately leading to tubulointerstitial fibrosis.

Albumins↗
PubMed2003

CD2-associated protein and glomerular disease.

CONTEXT: Proteinuria is a major cause of progression in renal disease. The glomerular ultrafiltration barrier, containing highly differentiated podocytes, normally restricts protein access to the urine. Patients with urinary protein in the nephrotic range (>3.5 g daily) often have effaced podocyte foot-processes. Slit diaphragms span the gaps between foot processes as a barrier to macromolecules. Nephrin and podocin are slit-diaphragm proteins identified in families with congenital nephrotic syndromes. CD2-associated protein (CD2AP) is an adapter protein originally identified as a novel ligand interacting with the T-cell-adhesion protein CD2. CD2AP knockout (-/-) mice develop a congenital nephrotic syndrome with podocyte foot-process effacements and die at 6 weeks of age from renal failure. CD2AP localises to the slit diaphragm and links nephrin and podocin to phosphoinositide 3-OH kinase; this complex has cell-signalling properties. STARTING POINT: The CD2AP +/- heterozygous mice developed by Jeong Kim and colleagues (Science 2003; 300: 1298-300) are haploinsufficient and develop glomerular changes at 9 months of age with a histological pattern similar to that in human focal segmental glomerulosclerosis. These researchers found that 2 of 30 African-American patients with idiopathic focal segmental glomerulosclerosis had a CD2AP mutation that ablated expression of one allele. WHERE NEXT? Further studies should address the normal distribution of the CD2AP heterozygous mutation in different ethnic populations, because the association with human idiopathic focal segmental glomerulosclerosis could be accidental. Decreased expression of CD2AP in podocytes of individuals with the CD2AP heterozygous mutation would help to understand how the haploinsufficiency translates into increased susceptibility to renal disease. Transfection of podocytes with mutated CD2AP or study of cultured podocytes from CD2AP +/- mice would provide further insight into whether the nephrin-podocin-CD2AP signal-transduction pathway is altered and leads to increased apoptosis of podocytes. Assuming that a decrease in CD2AP attenuates clearance of glomerular immune complexes, patients with other types of idiopathic glomerulonephritis should also have a CD2AP mutation. However, first studies looking at the most common form of glomerulonephritis, IgA nephropathy, have failed to show decreased renal CD2AP expression.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Growth factors and the development of diabetic nephropathy.

Growth factors play an important role in the development of functional and structural changes associated with diabetic nephropathy. Although it has been known for years that these factors are important for early renal hypertrophy and subsequent development of glomerulosclerosis and tubulointerstitial fibrosis, the exact molecular mechanism of many of these factors has only recently been more elucidated. Furthermore, growth factors also link the metabolic theory of diabetic complications with renal hemodynamic changes in diabetic nephropathy because some growth factors could directly influence glomerular hemodynamics and tubular transport in diabetic nephropathy. The high glucose environment with stimulated cellular uptake of glucose and accelerated nonenzymatic reactions resulting in Amadori-modified proteins and the later-developing advanced glycation end products are the main stimulators for intrarenal induction of growth factors. Intracellular generation of reactive species is an important signal intermediate in these stimulated expressions of growth factors. Taking into consideration the pivotal role of growth factors in the development of diabetic nephropathy, a therapeutic strategy to antagonize growth factor effects appears to be straightforward. However, the pleiotropic function of many of these factors and their physiologic role in normal renal homeostasis may make this approach difficult.

Animals↗
PubMed2003

Angiotensin II-induced hypertrophy of proximal tubular cells requires p27Kip1.

BACKGROUND: Angiotensin II (Ang II), as a single factor, induces hypertrophy of cultured proximal tubular cells of various species. Cells undergoing hypertrophy are arrested in the G1 phase of the cell cycle. Ang II also stimulated the expression of p27Kip1, an inhibitor of cyclin-dependent kinases (CDK). Although previous studies inhibiting p27Kip1 expression with antisense oligonucleotides suggested that this CDK inhibitor is important for Ang II-induced hypertrophy of proximal tubular cells, nonspecific effects of antisense technology, and the inability to transfect 100% of cells raised concerns about the true role of p27Kip1 in tubular hypertrophy. METHODS: Proximal tubular cells were isolated and cultured from wild-type (p27Kip1+/+) and knockout (p27Kip1-/-) mice. p27Kip1 genomic and protein expression was evaluated. Proximal tubular cell origin was confirmed by expression of various markers [3M-1 antigen, gamma-glutamyltransferase, angiotensin-converting enzyme (ACE)]. Cell proliferation (cell number, 3[H]thymidine incorporation) and hypertrophy (de novo protein synthesis as measured by 3[H]leucine incorporation, hypertrophy index, cell size) were evaluated. CDK2 and CDK4 activities were determined by an in vitro kinase assay. In addition, cell cycle analysis was performed by flow cytometry. p27Kip1 expression was reconstituted in two different clones of p27Kip1-/- proximal tubular cells using an inducible vector system based on ecdysone response elements. RESULTS: In accordance with previous studies, 10-7 mol/L Ang II induces hypertrophy and cell cycle arrest of p27Kip1+/+ proximal tubular cells. In contrast, Ang II facilitated cell cycle progression of two p27Kip1-/- proximal tubular cell lines without inducing hypertrophy. Ang II activates CDK4/cyclin D kinase activity in p27Kip1+/+ and -/- tubular cells, but stimulates CDK2/cyclin E activity only in wild-type cells. However, in the presence of Ang II, reconstituting p27Kip1 expression in p27Kip1-/- tubular cells using an inducible expression system, restored G1 phase arrest and the hypertrophic phenotype. Ang II did not induce apoptosis of either p27Kip1+/+ or -/- tubular cells. CONCLUSION: Our findings are the first clear evidence that p27Kip1 is required for Ang II-induced hypertrophy of proximal tubular cells. However, although p27Kip1 expression is an absolute requirement for this hypertrophy, reconstitution experiments revealed that other factors induced by Ang II contribute to this hypertrophy.

Angiotensin II↗
PubMed2003

Beneficial and adverse renal and vascular effects of the vasopeptidase inhibitor omapatrilat in renovascular hypertensive rats.

BACKGROUND: Vasopeptidase inhibitors are a new class of compounds that inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase. This study determined whether treatment with the vasopeptidase inhibitor omapatrilat (OMA) produced different effects on renal and cardiovascular structure compared with inhibition of ACE by enalapril (ENP) in rats with two-kidney, one clip hypertension (2K1C). METHODS: Hypertensive 2K1C rats were randomized into four groups and studied for another 8 weeks: no treatment, OMA, ENP or ENP combined with the diuretic hydrochlorothiazide (ENP + HCTZ). Albuminuria, vascular and renal histology as well as glomerular expression of transforming growth factor-beta (TGF-beta) were determined at the end of the experiment. RESULTS: OMA decreased blood pressure slightly better than ENP. However, combination of ENP with a diuretic lowered blood pressure equally effective as OMA. OMA was numerically more efficient in reducing cardiovascular and renal hypertensive changes compared with ENP. In contrast, the combination of ENP + HCTZ was as efficient as OMA. However, OMA lowered overexpression of TGF-beta in the non-clipped kidney better than ENP or ENP +HCTZ. Antihypertensive therapy surprisingly decreased renal function as shown by increased plasma creatinine and urea and decreased creatinine clearance. CONCLUSION: OMA is marginally more potent compared with ENP alone in lowering blood pressure and preventing cardiovascular and renal injury. This effect may be due to slightly better blood pressure reduction because addition of HCTZ enhances the cardio- and nephroprotective capacity of ENP. In contrast, OMA reduces TGF-beta overexpression in the non-clipped kidney better than ENP or ENP + HCTZ. Therefore, vasopeptidase inhibition is not superior to ACE inhibition in the prevention of cardiovascular and renal damage Goldblatt hypertension.

Analysis of Variance↗
PubMed2003

The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology.

The renal community is faced with an ever increasing number of patients reaching end-stage renal failure. Clinical studies have provided clear evidence that angiotensin-converting enzyme (ACE) inhibitors, and probably also AT1 receptor antagonists, at least in patients suffering from type 2 diabetes, slow disease progression to end-stage renal failure. This protective effect of drugs interfering with the renin-angiotensin system (RAS) are in part independent of reduction in systemic blood pressure, but involve normalization of glomerular hyperperfusion and hyperfiltration, restoration of altered glomerular barrier function, and reduction of stimulated tubular fluid reabsorption. Angiotensin II (ANG II) has emerged in the last decade as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. This review tries to bridge the classical hemodynamic actions of ANG II in the kidney with the more recently characterized effects of this vasopeptide. Finally, clinical implications are suggested based on data from clinical studies. A thorough understanding of the RAS is important to recognize the potential of nephroprotective strategies through inhibition of its components.

Animals↗
PubMed2003

Extracellular actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis.

Exogenous administration of actin prevents tumour growth in mice by specifically antagonizing angiogenin, a potent inducer of neovascularization. To investigate whether the angiogenin/actin system is also of importance in renal disease, we examined the effect of actin during glomerular capillary repair in anti-Thy-1.1 mesangioproliferative glomerulonephritis. Male Wistar rats were injected intravenously with actin, a control protein, i.e. albumin, or vehicle alone at 8, 16, 24, 32, 40 and 48 h after disease induction. On day 8, actin-treated rats showed significantly more microaneurysms and persistent mesangiolysis as compared to both control groups. This was associated with increased proteinuria in actin-treated rats. Moreover, actin-treated rats showed increased counts of glomerular macrophages (+40%) and polymorphonuclear leukocytes (+100%) on day 3 as well as a decrease in glomerular endothelial area on days 3 and 8. However, no difference in early glomerular endothelial as well as non-endothelial cell proliferation was noted in actin-treated rats as compared to controls. Actin treatment had no apparent influence on mesangial cell activation (i.e. de novo expression of alpha-smooth muscle actin) or glomerular accumulation of fibronectin or type IV collagen. Additional in vitro studies demonstrated that extracellular actin inhibits the angiogenin but not VEGF(165)-induced proliferation of (glomerular) endothelial cells. Moreover, actin inhibited other, yet unidentified, serum-derived angiogenic factors. In conclusion, exogenous actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis possibly due to interference with angiogenic factors such as angiogenin. Our combined in vivo and in vitro observations suggest that the release of intracellular actin during mesangiolysis is an endogenous pathway by which glomerular capillary damage is augmented.

Actins↗
PubMed2003

Cell cycle control in glomerular disease.

Glomerular diseases are a leading caused of kidney failure. The three resident glomerular cell types respond differently to injury, which includes proliferation, hypertrophy, apoptosis and de-differentiation. Each leads to glomerular scarring, and a decline in renal function. Studies have shown that these events are critically controlled by cell cycle regulatory proteins, providing potential targets for the development of future therapeutics.

Animals↗
PubMed2002

Induction of p27KIP1 after unilateral ureteral obstruction is independent of angiotensin II.

BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by proliferation of tubular and interstitial cells, and infiltration of the renal parenchyma with macrophages/monocytes. These alterations lead ultimately to tubulointerstitial fibrosis and tubular atrophy. Some of these changes are caused by an activated renin-angiotensin system (RAS). We have previously demonstrated that angiotensin II induces the expression of the cell cycle inhibitor p27KIP1 in cultured tubular cells. The current study tested the hypothesis that interference with the RAS may modulate renal expression of p27KIP1 after UUO. METHODS: The ureter of the left kidney of Sprague-Dawley rats was ligated. Sham-operated animals served as controls. Rats were randomized in four groups and received one of the following: no therapy, enalapril, losartan, or triple therapy (hydralazine, reserpine, hydrochlorothiazide). Kidneys were removed and cortical protein lysates were prepared for the detection of p27KIP1 by Western blotting. Immunohistochemistry was performed for p27KIP1, PCNA, ED-1, and alpha-smooth muscle actin. Apoptosis was quantified by TUNEL-staining. RESULTS: p27KIP1 expression as detected by Western blotting reached a maximum 10 days after UUO. Tubular and interstitial cells contributed to this increase in p27KIP1 expression whereas the number of glomerular p27KIP1 positive cell did not change. p27KIP1-positive cells were macrophages/monocytes (positive ED-1 staining) or had the characteristics of myofibroblasts (positive alpha-smooth muscle actin staining). Tubular and interstitial proliferation [proliferating cell nuclear antigen (PCNA)-positive staining] and apoptosis [terminal deoxy transferase uridine triphosphate nick end labeling (TUNEL) staining] also was increased after UUO. However, individual cells stained either positive for p27KIP1 or PCNA, but not both. Although enalapril and losartan reduced the number of macrophages/monocytes and attenuated the degree of tubular and interstitial apoptosis, these drugs did not influence p27KIP1 expression. There was no change in the number of p27KIP1-positive cells in the contralateral kidney undergoing hypertrophy. CONCLUSION: Induction of p27KIP1 in this model represents an endogenous response to likely limit proliferation that is independent of angiotensin II. Since there was no close correlation between apoptosis and p27KIP1 expression, it may be that the overall number of p27KIP1 expressing cells sets a general restriction point for apoptosis rather than defines an individual level of cell fate.

Actins↗
PubMed2002

Angiotensin II infusion ameliorates the early phase of a mesangioproliferative glomerulonephritis.

BACKGROUND: Inhibition of the renin-angiotensin system slows the progression of chronic renal disease. METHODS: To test whether angiotensin II (Ang II) infusion aggravates or ameliorates an acute glomerulonephritis, the peptide was infused (200 ng/min by osmotic minipump) in rats with an anti-thymocyte antibody-induced glomerulonephritis (ATS). RESULTS: Ang II significantly increased blood pressure. Following injection of the antibody, similar glomerular binding of rabbit IgG and rat complement C3 was detected in ATS and Ang II+ATS rats, indicating no differences in delivery and binding of the antibody. Ang II infusion, however, induced a significant reduction in glomerular monocyte infiltration, cell proliferation and matrix expansion in nephritic rats compared to rats with nephritis without Ang II. The antiproliferative effect of Ang II was inhibited by the Ang II type 1 (AT1) receptor blocker irbesartan, but not by the AT2 receptor blocker PD 123319, indicating that this effect was likely transduced by AT1 receptors. Norepinephrine infusion (600 ng/min) produced a similar degree of hypertension, but did not affect glomerular proliferation in nephritic rats. Ang II induced the glomerular expression of the cell cycle inhibitor p27KIP1 and of transforming growth factor-beta (TGF-beta) and inhibited expression of monocyte chemotactic protein 1 (MCP-1). CONCLUSION: Ang II surprisingly ameliorates glomerular monocyte infiltration, proliferation and matrix expansion in ATS nephritis. Ang II-mediated induction of cyclin kinase inhibitors and TGF-beta may contribute to the protection of the glomerulus from inflammatory injury by inducing cell cycle arrest and attenuating activation of local and recruited cells. Alternatively, Ang II might protect the kidney at least in part by less inflow of disease activators due to reduction of renal blood flow. Therefore, activation of the renin-angiotensin system may have protective effects in certain pathophysiological situations.

Angiotensin II↗
PubMed2002

Chronic anti-Thy-1 nephritis is aggravated in the nonclipped but not in the clipped kidney of Goldblatt hypertensive rats.

BACKGROUND: We have previously shown that renovascular hypertension does not inhibit healing of the acute Thy-1 nephritis. To test whether a chronic model of the Thy-1 nephritis is more susceptible to high blood pressure, the repetitive hit model was evaluated in rats with 2-kidney, 1-clip Goldblatt hypertension. METHODS: Six weeks after initiation of 2-kidney, 1-clip hypertension, chronic Thy-1 glomerulonephritis was induced in hypertensive rats by four consecutive injections of rabbit antiserum in weekly intervals. Renal structure and function were examined two weeks after the last injection. Glomerular binding of rabbit IgG as well as expression of transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin (alpha-SMA) and cyclooxygenase (COX)-1 and -2 were evaluated by Western blotting. RESULTS: Similar glomerular deposition of rabbit IgG was detected in normotensive rats and in both kidneys of Goldblatt hypertensive rats indicating similar delivery and binding of the heterologous antibody. Induction of the repetitive Thy-1 model significantly enhanced glomerular damage in the nonclipped kidney and increased albuminuria. Surprisingly, no glomerular damage developed in the clipped kidney of nephritic hypertensive rats. In contrast, increased glomerular volume and increased expression of TGF-beta, alpha-SMA as well as COX-1 and COX-2 were found in normotensive nephritic rats and in both kidneys of nephritic hypertensive rats. CONCLUSION: Glomerular and tubulointerstitial damage of the chronic Thy-1 model is dramatically enhanced in the nonclipped kidneys of Goldblatt hypertensive rats. In contrast, the clipped kidney is completely protected from this immunological injury despite similar activation of glomerular cells, induction of TGF-beta, COX-1 and COX-2 and glomerular hypertrophy.

Albuminuria↗
PubMed2002

Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors.

BACKGROUND: Recent evidence suggests that angiotensin II (Ang II) induces a variety of proinflammatory mediators including chemokines. Nuclear factor-kappaB (NF-kappaB) activation plays an important role in Ang II-mediated inflammation. The present study investigated which Ang II receptor subtype is involved in NF-kappaB activation. We focused particularly on the Ang II subtype 2 (AT2) receptor because we previously observed that Ang II-induction of the chemokine RANTES in vitro and in vivo is mediated through AT2 receptors. METHODS: AT1 or AT2 receptors were selectively overexpressed in COS7 cells that normally do not express Ang II receptors. In addition, rat glomerular endothelial cells (GER) that express AT1 and AT2 receptors and PC12 cells that exclusively exhibit AT2 receptors were studied also. Ang II-receptor expression was confirmed by Western blots of membrane lysates. NF-kappaB DNA binding in vitro was detected by electrophoretic shift assays. In addition, in vivo transactivation of a reporter gene construct with kappa enhancer coupled to luciferase also was investigated. Expression of the inhibitor of kappaB alpha (IkappaB-alpha) was detected by Western blots. RESULTS: In AT1 or AT2 receptor transfected cells, but not untransfected COS7 cells, 10-7 mol/L Ang II induced NF-kappaB DNA binding in vitro, as detected by electrophoretic shift assays and in vivo transactivation of a reporter gene construct. The AT2 receptor antagonist PD 123319 but not losartan attenuated Ang II-mediated NF-kappaB activation in COS7 cells transfected with AT2 receptors. While Ang II also induced NF-kappaB activation in PC12 cells, this activation was blocked by PD 123319. Finally, stimulation of GERs with Ang II led to the activation of NF-kappaB through both subtypes of Ang II receptors. Nuclear extracts from COS7 cells transfected with AT2 receptors and PC12 cells with NF-kappaB DNA-binding activity consisted of p50/p65 complexes. There was no difference in subunit composition of nuclear proteins from Ang II-stimulated AT1 receptor transfected COS7 cells. An artificial peptide (p-Amino-Phe6-Ang II) with a high affinity for the AT2 receptor also activated NF-kappaB. Ang II-induced activation of NF-kappaB was associated with degradation of IkappaB-alpha in all studied cell lines. CONCLUSIONS: Our results clearly demonstrate in various cell lines that Ang II induces NF-kappaB activation through AT2 receptors. These data may have important therapeutic consequences, because potential Ang II-mediated proinflammatory renal and cardiovascular effects may not be totally antagonized by the currently increased clinical use of AT1 receptor antagonists.

Angiotensin II↗
PubMed2002

Effects of different PPARgamma-agonists on MCP-1 expression and monocyte recruitment in experimental glomerulonephritis.

BACKGROUND: Activators of peroxisome proliferator activated receptor gamma (PPARgamma) have been shown to modulate chemokine expression in isolated monocytes/macrophages (M/M) and to exert anti-inflammatory effects in some models of experimental inflammatory diseases. We evaluated the effects of different forms of PPARgamma activators in a model of experimental glomerulonephritis (GN) in rats. METHODS: GN was induced in rats by application of an anti-thymocyte antibody (ATS). Nephritic rats were treated with two synthetic PPARgamma ligands of the thiazolidinedione (TZD) group, troglitazone (200 mg/kg/day) and ciglitazone (100 mg/kg/day), and with a natural ligand 15d-PGJ2 (1.5 mg/day). Twenty-four hours after induction of the GN, the glomerular mRNA expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) and the cognate chemokine receptor CCR-2 were examined by Northern blotting and RT-PCR. The glomerular M/M infiltration was determined by immunohistology. The activation of the transcription factors PPARgamma, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) in glomeruli was analyzed by electrophoretic mobility shift assay. RESULTS: Induction of GN up-regulated glomerular nuclear protein binding of NF-kappaB and AP-1. Treatment of nephritic rats with troglitazone and ciglitazone augmented nuclear PPARgamma and AP-1 DNA binding but did not affect NF-kappaB binding. TZD enhanced glomerular MCP-1 expression and increased glomerular M/M recruitment. In contrast, 15d-PGJ2 attenuated NF-kappaB activation and did not affect AP-1 activity or MCP-1 expression. CONCLUSION: Our data show that PPARgamma activators of the TZD group, but not 15d-PGJ2, enhance MCP-1 expression and M/M infiltration in the induction phase of experimental GN. The results demonstrate that TZD and 15d-PGJ2 may exert different effects in the immune response in experimental GN. Our study underscores the need to critically evaluate whether PPARgamma ligands will have beneficial or possibly deleterious effects in GN.

Animals↗