Abstract
Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR. Kidney biopsies of DN patients and health individuals were stained by immunofluorescence (IF) method. The morphological and functional changes of podocytes were tested by F-actin staining and cell migration assay. Results demonstrated that HG induced upregulation of UCH-L1 and activation of the Wnt/β-catenin signaling pathway in podocytes. However, blocking of the Wnt pathway by dickkopf related protein 1 (DKK1) eliminated the above changes. Furthermore, IF staining confirmed that, compared with healthy individuals, the expression of UCH-L1 and β-catenin were obviously increased in kidney biopsy of DN patients. Overexpression of UCH-L1 remodeled its actin cytoskeleton, increased its cell migration and impacted its important proteins. All the findings manifested that Wnt/β-catenin/UCH-L1 may be a new potential therapy method in the treatment of DN in future.
Highlights
Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM)
The detectable early marker of DN is the appearance of microalbuminuria, followed by proteinuria, hyperfiltration, and up to reductions in the glomerular filtration rate, which manifests the destruction of the glomerular filtration barrier (GFB)
At the mRNA level, quantitative real time reverse transcribed (RT)-PCR showed the increase of ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) in high glucose (HG)-treated cells were greater than that in the control group, ~4.4-fold for 48 h (Figure 1C)
Summary
Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM). The detectable early marker of DN is the appearance of microalbuminuria, followed by proteinuria, hyperfiltration, and up to reductions in the glomerular filtration rate, which manifests the destruction of the glomerular filtration barrier (GFB). Podocytes are terminally differentiated epithelial cells locating in the inner layer of Bowman’s capsule that constitute the outer layer of GFB. Their normal structure and function play a major role in maintaining normal integrity of the GFB, which explain why podocyte injury is generally associated with increasing obvious proteinuria [1]. The mechanisms of podocyte injury induced by HG are not well explored
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