Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

Abstract

Aims/Introduction: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. Materials and Methods: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10 -7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10 -6 mol/L) or autophagy inducer, rapamycin (10 -3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/ SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. Results: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV.Conclusions: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.

Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease

“…Urotensin II has also been implicated in pancreatic beta-cell dysfunction and in diabetic retinopathy. Marked elevated levels of urotensin II and urotensin II receptor, also known as GPR14 expression have been observed in renal biopsies of patients with DKD [115][116][117]. This finding was further supported in animal experiments suggesting urotensin II/GPR14 as a mediator of renal fibrosis [118].…”