Jingsong Liu1, Ying Zhong1, Guoyong Liu2, Xiaobai Zhang1, Bofei Xiao1, Shang Huang1, Hong Liu3, Liyu He3. 1. Department of Nephrology, Hospital affiliated to Hunan Academy of Chinese Medicine, Chinese Medicine and Western Medicine Hospital affiliated to Hunan University of Chinese medicine, Changsha, China. 2. Department of Nephrology, the First Affiliated Hospital of Changde Vocational Technical College, Changde, China. 3. Department of Nephrology, The Second Xiangya Hospital of Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, China.
Abstract
BACKGROUND/AIMS: Transforming growth factor β 1 (TGFβ1) plays a critical role in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs) during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. METHODS: Expression of TGFβ1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO) in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFβ1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. RESULTS: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFβ1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. CONCLUSION: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.
BACKGROUND/AIMS: Transforming growth factor β 1 (TGFβ1) plays a critical role in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs) during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. METHODS: Expression of TGFβ1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO) in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFβ1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. RESULTS: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFβ1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. CONCLUSION: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.
Authors: Liu Feng; Wang Li; Yu Chao; Qin Huan; Fang Lu; Wang Yi; Wang Jun; Cui Binbin; Liu Na; Zhuang Shougang Journal: Kidney Dis (Basel) Date: 2020-08-23