Suppression of experimental crescentic glomerulonephritis by peroxisome proliferator-activated receptor (PPAR) γ activators

最近有报道称过氧化物酶体增殖物激活受体(PPAR) γ具有抗炎作用。一些报道表明PPAR γ对肾细胞有影响，但确切的知识有限。首先，我们检测了PPARg激活剂对克隆肾细胞（LLC-PK1）凋亡的影响，RT-PCR显示了PPARg在LLC-PK1细胞中的表达。ppar配体如曲格列酮、BRL49653和15-脱氧- δ -12,14-前列腺素J2抑制血清剥夺诱导的细胞凋亡。PPARa激活剂没有模仿曲格列酮的效果。曲格列酮的抗凋亡作用可被磷脂酰肌醇-3激酶（PI3K）抑制剂wortmannin部分阻断，而其他激酶抑制剂则不能。此外，我们发现曲格列酮增加了c-myc的表达，据报道，在其他系统中，c-myc在缺乏血清的情况下会导致细胞凋亡。而bcl-2的表达不受影响。这些结果表明，PPARg的激活对lc - pk1细胞通过PI3K途径被剥夺血清诱导的细胞凋亡具有抑制作用。注射兔抗大鼠肾小球基底膜抗体诱导WKY大鼠继发性月牙状肾小球肾炎。曲格列酮可抑制尿蛋白排泄和新月形成，如新月评分所示。吡格列酮的作用类似于曲格列酮，而PPAR α-活化剂则没有。免疫组织学显示，曲格列酮和吡格列酮抑制ed -1阳性单核/巨噬细胞和cd8阳性细胞向肾小球的浸润。在本研究中，我们证明了PPAR γ激活剂通过PPAR依赖机制抑制炎症细胞的募集来发挥抗肾病作用。综上所述，在肾细胞中，PPARγ-激活剂可抑制体外培养的肾细胞凋亡并抑制实验性大鼠肾小球肾炎，PPARγ-依赖性机制可能在肾细胞中起重要作用。少

It has been recently reported that peroxisome proliferator-activated receptor (PPAR) γ exhibits anti-inflammatory effects. A couple of reports suggests effects of PPAR γon kidney cells, but precise knowledge are limited.First, we examined the effects of PPARg activators on the apoptosis of clonal kidney cells (LLC-PK1), RT-PCR revealed the expression of PPARg in LLC-PK1 cells. The ligands for PPARg such as troglitazone, BRL49653 and 15-deoxy-delta-12,14-prostaglandin J2 inhibited serum-deprivation-induced apoptosis of the cells. PPARa activators did not mimic the effect of troglitazone. Antiapoptotic effects of troglitazone were partially blocked by a phosphatidyl-inositol-3 kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors. Further, we showed that troglitazone increased the expression of c-myc which was reported to cause apoptosis in the absence of serum in other systems. However, the expression of bcl-2 was not affected. These results suggest that the activation … More of PPARg has an inhibitory effect on the apoptosis induced by serum deprivation through the PI3K pathway in LLC-PK1 cells.Secondary, crescentic glomerulonephritis was induced by the injection of rabbit anti-rat glomerular basement membrane antibody in WKY rats. Administration of troglitazone suppressed urinary protein excretion and crescent formation as indicated by crescent scores. Pioglitazone mimicked the effect of troglitazone, but PPAR α-activators did not. Immunohistology revealed that troglitazone and pioglitazone inhibited the infiltration of ED-1-positive monocyte/macrophages and CD8-positive cells into glomeruli. In the present study, we demonstrated that PPAR γ activators exert antinephritic effects by suppressing the recruitment of inflammatory cells via PPARg-dependent mechanism.In conclusion, in kidney cells, PPAR γ-activators inhibits apoptosis of cultured kidney cells in vitro and suppresses experimental glomerulonephritis in rats, PPARγ-dependent mechanism may have a important role in kidney cells. Less