The Wnt Signaling Pathway in Diabetic Nephropathy.

Haiying Wang,Jingsuo Wang,Jinxiang Yuan,Yawen Zhang,Wei Ji,Ran Zhang,Xinjie Wu,Yiqun Tang,Yafen Chen,Yong Xia

doi:10.3389/fcell.2021.701547

Abstract

Diabetic nephropathy (DN) is a serious kidney-related complication of both type 1 and type 2 diabetes mellitus (T1DM, T2DM) and the second major cause of end-stage kidney disease. DN can lead to hypertension, edema, and proteinuria. In some cases, DN can even progress to kidney failure, a life-threatening condition. The precise etiology and pathogenesis of DN remain unknown, although multiple factors are believed to be involved. The main pathological manifestations of DN include mesangial expansion, thickening of the glomerular basement membrane, and podocyte injury. Eventually, these pathological manifestations will lead to glomerulosclerosis, thus affecting renal function. There is an urgent need to develop new strategies for the prevention and treatment of DN. Existing evidence shows that the Wnt signaling cascade plays a key role in regulating the development of DN. Previous studies focused on the role of the Wnt canonical signaling pathway in DN. Subsequently, accumulated evidence on the mechanism of the Wnt non-canonical signaling indicated that Wnt/Ca2+ and Wnt/PCP also have essential roles in the progression of DN. In this review, we summarize the specific mechanisms of Wnt signaling in the occurrence and development of DN in podocyte injury, mesangial cell injury, and renal fibrosis. Also, to elucidate the significance of the Wnt canonical pathway in the process of DN, we uncovered evidence supporting that both Wnt/PCP and Wnt/Ca2+ signaling are critical for DN development.

Highlights

Diabetic nephropathy (DN) is the most common form of secondary kidney disease that leads to end-stage renal disease (Kawanami et al, 2016)
The pathogenesis of DN characterized by mesangial expansion, podocyte injury, basement membrane thickening, glomerular and renal tubular cell injury is complex and diverse, all of those damage to renal tissues eventually lead to glomerulosclerosis and interstitial fibrosis
Wnt canonical signal plays a key role in the occurrence and development of DN

Summary

Introduction

Diabetic nephropathy (DN) is the most common form of secondary kidney disease that leads to end-stage renal disease (Kawanami et al, 2016). The canonical Wnt/β-catenin pathway plays an important role in regulating gene transcription (MacDonald et al, 2009). According to a previous study, the abnormal up-regulation of the Wnt/β-catenin signaling pathway leads to podocyte damage and dysfunction (Dai et al, 2009) (Supplementary Figure S2).

Results

Conclusion