Effect of TGF-β/Smad signal pathway mediated by integrin linked kinase in the progress of renal fibrosis
10.3969/j.issn.1671-8348.2015.28.005
- VernacularTitle:ILK 介导 TGF-β／Smad 通路诱导肾小球内皮细胞-间充质细胞转分化的研究
- Author:
Lin LIN
;
Jing ZHENG
;
Weiping ZHU
- Publication Type:Journal Article
- Keywords:
integrin linked kinase;
human glomerular endothelial cells;
endothelial-mesenchymal transition;
transforming
- From:
Chongqing Medicine
2015;(28):3911-3914
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of TGF‐β1 in the endothelial‐mesenchymal transition EndM T of glomeruli ,and to explore the effect of TGF‐β/Smad signaling pathway mediated by integrin linked kinase(ILK ) in the progress of renal fibrosis . Methods Human glomerular endothelial cells (HGEnC) incubated in vitro were divided into blank control group ,TGF‐β1 (12 .5 , 25 .0 ,50 .0 ng/mL) group .TGF‐β1 50 .0 ng/mL receptor type one antagonist (LY364749)5 .0 μmol/L group ,ILK (QLT‐0267)5 .0μmol/L antagonist group .The mRNA level of P‐Smad 2/3 and ILK was determined by RT‐PCR ,and the protein level of P‐Smad 2/3 ,ILK ,E‐cadherin ,CD31 ,α‐SMA and FSP‐1 was determined by Western blot after 48 h and 72 h after incubation in each group un‐der the above‐mentioned condition .Results (1)TGF‐β1 could significantly increased the mRNA level of P‐Smad2/3 and ILK (P<0 .01) ,and the protein level of P‐Smad2/3 ,ILK ,E‐cadherin ,CD31 ,α‐SMA as well as FSP‐1 (P < 0 .01) in the concentration‐de‐pendent manner ,but significantly decreased the protein level of E‐cadherin and CD31 ( P < 0 .01) in the concentration‐dependent manner ;(2)TGF‐β1 receptor type one antagonist and ILK antagonist significantly inhibited the increasing mRNA level of ILK (P<0 .01) ,and the protein level of ILK ,E‐cadherin ,CD31 ,α‐SMA as well as FSP‐1 (P< 0 .01) induced by TGF‐β1 in the concentration‐dependent manner ,and significantly inhibited the decreasing protein level of E‐cadherin and CD31 induced by TGF‐β1 in the concen‐tration‐dependent manner(P< 0 .01) ;(3)TGF‐β1 receptor type one antagonist significantly inhibited the increasing mRNA and pro‐tein level of P‐Smad2/3(P< 0 .01) ,but ILK antagonist had no effect to the increased mRNA and protein level of P‐Smad2/3 (P>0 .05) .Conclusion TGF‐β1 as the effector molecule in downstream can promote endothelial‐mesenchymal transition of HGEnC ,and TGF‐β/Smad signaling pathway mediated integrin linked kinase participate in this process ,which probably play important role in the progress of renal fibrosis .
