Role Of Insulin-like Growth Factor-1 In The Pathogenesis Of Autosomal Dominant Polycystic Kidney Disease

Objective To explore the role of insulin-like growth factor-1i n pathogenesis of autosomal dominant polycystic kidney disease. Methods IGF-1 levels in plasma urine and cystic fluid from 41 case of ADPKD patients were determined by ELISA; The expressi on of IGF-1 and IGF-1R, IGF-lmRNA IGF-lRmRNA were detect ed inADPKD kidney tissues and normal kidney tissues using imm unohistochemistry and in situ hybridization technique. Using MTT, flow cytometry analysis and electronic microscopy ,the effect of I GF-1 on proliferation of LLC-PK1 MDCK were examined;The exp ression of c-fos,c-jun, bcl-2,bax in proliferation of LLC-PK1,MDC K stimulated by 20ng/ml IGF-1 were detected by immoncytochemi stry.Result The level of IGF-1 in cystic fulid from41 case of AD PKD patients was higher than those in plasma and urine (162 + 5. 064 vs 76 + 28.137 p<0.01; 162 + 5.064 vs 62+ 19.180)ng/ml,p<0.0 l.Thepositive expression of IGF-lRmRNA, IGF-1R in normal kidn ey tissues was mostly located in distal convoluted tubules. The ex pression of IGF-land IGF-1R in cyst lining-epitheliar cells ,smoot h muscle cells ,interstitial cells in ADPKD kidney tissues was si gnificantly increased compared with that of normal kidney tissues (IGF-10.78+0.058 vs 0.38+0.024;IGF-1R0.72+0.093 vs0.38+0.034)ng /ml p<0.01.The positive expression of IGF-1 mRNAv IGF-1 and IGF -1RmRNA IGF-1R was mostly distributed in cystic tissues (IGF-1mRNA 0.55+0.087 vs 0.28+0.039; IGF-lRmRNA 0.53+0.036 vsO.30 +0.086 p<0.01),but The positive expression of IGF-lmRNA, IGF-1in normal kidney tissues was located in proximal convoluted tub ules. the proliferation of LLC-PK1 and MDCK were markedly pro moted by l~50ng/ml IGF-1, and the ratio of S phase in cell cyclewas elvated. the expression of c-fos and c-jun was markedly incr eased while bcl-2 significantly increased, bax decreased after addi ng 20ng/ml IGF-1 into culture medium. Conclusion The synthesisand secreting of IGF-1 by cyst lining-epitheliar cells and intersti tial cells increases significantly by autocrine and paracrine, IGF-1 stimulates proliferation of cyst lining-epitheliar cells and inhibitesthe cell apotosis may be one of pathogenesis of the renal cyst f ormation and development in ADPKD.