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

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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

Diagram shows the Wnt/β-catenin/UCH-L1 signaling leading to podocyte injury in HG environment. HG induces Wnt5, activates β-catenin, and elevates UCH-L1, followed by changes of F-actin, hypermotility and changes of some proteins, which can be blocked by DKK1.
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ijms-17-01404-f008: Diagram shows the Wnt/β-catenin/UCH-L1 signaling leading to podocyte injury in HG environment. HG induces Wnt5, activates β-catenin, and elevates UCH-L1, followed by changes of F-actin, hypermotility and changes of some proteins, which can be blocked by DKK1.

Mentions: In this study, results demonstrated that HG upregulated the expression of UCH-L1 in murine podocytes, which might be mediated by the Wnt/β-catenin signaling pathway. Furthermore, IF results proved such close relationship between β-catenin and UCH-L1 in DN patients. The overexpression of UCH-L1 not only changed F-actin and hypermotility of podocytes but also changed several important proteins (Figure 8). All the above findings illustrated that the Wnt/UCH-L1 may present a new injury mechanism of DN.


Wnt/ β -Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy
Diagram shows the Wnt/β-catenin/UCH-L1 signaling leading to podocyte injury in HG environment. HG induces Wnt5, activates β-catenin, and elevates UCH-L1, followed by changes of F-actin, hypermotility and changes of some proteins, which can be blocked by DKK1.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01404-f008: Diagram shows the Wnt/β-catenin/UCH-L1 signaling leading to podocyte injury in HG environment. HG induces Wnt5, activates β-catenin, and elevates UCH-L1, followed by changes of F-actin, hypermotility and changes of some proteins, which can be blocked by DKK1.
Mentions: In this study, results demonstrated that HG upregulated the expression of UCH-L1 in murine podocytes, which might be mediated by the Wnt/β-catenin signaling pathway. Furthermore, IF results proved such close relationship between β-catenin and UCH-L1 in DN patients. The overexpression of UCH-L1 not only changed F-actin and hypermotility of podocytes but also changed several important proteins (Figure 8). All the above findings illustrated that the Wnt/UCH-L1 may present a new injury mechanism of DN.

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