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Wnt/ β -Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Effect of UCH-L1 overexpression on structure injury in podocytes. Immunofluorescence staining of F-actin was performed in podocytes of control group, control infection group and UCH-L1 infection group. F-actin was showed in red, cell nucleus showed with DAPI in blue (n = 5). Original magnification, 200×.
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ijms-17-01404-f005: Effect of UCH-L1 overexpression on structure injury in podocytes. Immunofluorescence staining of F-actin was performed in podocytes of control group, control infection group and UCH-L1 infection group. F-actin was showed in red, cell nucleus showed with DAPI in blue (n = 5). Original magnification, 200×.

Mentions: To investigate the effect of increased UCH-L1 to podocyte structure in vivo, cytoskeleton was stained with F-actin staining in UCH-L1 adenoviral vector-infected podocytes and control group and control infection group. As the results shown in Figure 5, in both control groups podocytes displayed an obvious multiple-process morphological structure, and all the actin fibers arranged in order as nearly paralleled fasciculate models in the cytoplasm. In contrast, in UCH-L1 adenoviral vector-infected podocytes, the morphology of podocytes significantly changed. The thin process became less and the actin fibers became out-of-order and intertwined with each other, which were mostly around the nucleus. These results indicated that UCH-L1 overexpression could change podocytes morphological structure.


Wnt/ β -Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy
Effect of UCH-L1 overexpression on structure injury in podocytes. Immunofluorescence staining of F-actin was performed in podocytes of control group, control infection group and UCH-L1 infection group. F-actin was showed in red, cell nucleus showed with DAPI in blue (n = 5). Original magnification, 200×.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037684&req=5

ijms-17-01404-f005: Effect of UCH-L1 overexpression on structure injury in podocytes. Immunofluorescence staining of F-actin was performed in podocytes of control group, control infection group and UCH-L1 infection group. F-actin was showed in red, cell nucleus showed with DAPI in blue (n = 5). Original magnification, 200×.
Mentions: To investigate the effect of increased UCH-L1 to podocyte structure in vivo, cytoskeleton was stained with F-actin staining in UCH-L1 adenoviral vector-infected podocytes and control group and control infection group. As the results shown in Figure 5, in both control groups podocytes displayed an obvious multiple-process morphological structure, and all the actin fibers arranged in order as nearly paralleled fasciculate models in the cytoplasm. In contrast, in UCH-L1 adenoviral vector-infected podocytes, the morphology of podocytes significantly changed. The thin process became less and the actin fibers became out-of-order and intertwined with each other, which were mostly around the nucleus. These results indicated that UCH-L1 overexpression could change podocytes morphological structure.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus