Abstract
Progressive reduction of SnoN is associated with gradual elevation of TGF-β1 during diabetic nephropathy progression, suggesting SnoN to be a possible mediator of TGF-β1 signaling, with potential therapeutic benefits against TGF- β1 –induced renal fibrosis. To characterize SnoN for its role in renal fibrosis, we assessed SnoN expression patterns in response to high glucose stress, and evaluated the effects of upregulating SnoN on renal fibrosis. High glucose stress induced significantly elevated SnoN, TGF-β1, and Arkadia transcription; however, significantly reduced SnoN protein levels were observed under these conditions. Upregulating the SnoN protein was achieved by Arkadia knockdown, which resulted in inhibited high glucose-induced epithelial-mesenchymal transition (EMT) in renal tubular cells, the onset phase of renal fibrosis. Alternatively, EMT was suppressed by dominantly expressed exogenous SnoN without interfering with TGF-β1. Overall, renal SnoN upregulation ameliorates renal fibrosis by relieving high glucose-induced EMT; these findings support a translational approach targeting SnoN for the treatment of diabetic nephropathy.
Highlights
Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, and evolves progressively toward end-stage renal failure (ESRF)
epithelial-mesenchymal transition (EMT) progression involves multiple factors interacting with TGF-β1/Smad signaling, directly or not
Tracking EMT markers and understanding the factors involved in TGF-β1/Smad signaling can help evaluate renal fibrosis treatment [17,18]
Summary
Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, and evolves progressively toward end-stage renal failure (ESRF). DN is the major contributor to chronic renal failure and leading cause of death in diabetic patients [1]. Renal tubulointerstitial fibrosis is one of the distinct features for pathological diagnosis of DN. Multiple factors, including vasoactive substances, chemokines, cytokines, and growth factors, are involved in hyperglycemia triggered DN progression, with TGF-β1 and its co-factors playing critical roles [2,3,4]. The significant increase of TGF-β1 in various renal cells, such as mesangial-, tubular epithelial-, vascular endothelial-, smooth muscle-, and interstitial cells, is associated with pathological.
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