Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):289-296. doi: 10.26355/eurrev_201901_16775.
To explore the specific role of ILK (integrin-linked kinase) in regulating renal fibrosis and its underlying mechanism.
NRK-52E cells were induced by transforming growth factor-β1 (TGF-β1) for observing phenotype change. Renal tubular epithelial cell marker, fibrosis marker and expression level of ILK in NRK-52E cells were also detected. After overexpression of ILK, phenotype change of NRK-52E cells was observed. For in vivo experiments, we constructed UUO (unilateral ureteral obstruction) model in CD1 mice. Renal tubular epithelial cell marker, fibrosis marker and expression level of ILK in UUO mice were detected. The regulatory effect of ILK on renal fibrosis was detected after injection of ILK overexpression plasmid. Western blot was performed to detect related genes in the TGF-β1/smad pathway.
Accompanied by the TGF-β1-induced phenotype change in NRK-52E cells, both mRNA and protein levels of ILK were upregulated. Overexpression of ILK remarkably stimulated the phenotype change in NRK-52E cells. Similarly, ILK was highly expressed in UUO mice. Renal fibrosis was aggravated after injection of ILK overexpression plasmid in UUO mice. Western blot results showed that expressions of p-smad3 and smad3 were upregulated during the process of renal fibrosis.
ILK is upregulated during the process of renal fibrosis. ILK participates in the development of renal fibrosis by altering phenotypes of renal tubular epithelial cells via a TGF-β1/smad pathway.
探讨整合素连接激酶（ILK）在调节肾纤维化中的具体作用及其潜在机制。
用转化生长因子-β1（TGF-β1）诱导 NRK-52E 细胞，观察其表型变化。检测 NRK-52E 细胞中肾小管上皮细胞标志物、纤维化标志物和 ILK 的表达水平。过表达 ILK 后，观察 NRK-52E 细胞的表型变化。构建单侧输尿管梗阻（UUO）模型，在 CD1 小鼠体内实验，检测 UUO 小鼠中肾小管上皮细胞标志物、纤维化标志物和 ILK 的表达水平。注射 ILK 过表达质粒后，检测 ILK 对肾纤维化的调节作用。采用 Western blot 检测 TGF-β1/smad 通路相关基因。
随着 TGF-β1 诱导的 NRK-52E 细胞表型变化，ILK 的 mRNA 和蛋白水平均上调。过表达 ILK 显著刺激 NRK-52E 细胞的表型变化。同样，ILK 在 UUO 小鼠中高表达。在 UUO 小鼠中注射 ILK 过表达质粒后，肾纤维化加重。Western blot 结果显示，在肾纤维化过程中，p-smad3 和 smad3 的表达上调。
ILK 在肾纤维化过程中上调。ILK 通过 TGF-β1/smad 通路改变肾小管上皮细胞的表型，参与肾纤维化的发生发展。
