Peroxisome Proliferator-Activated Receptor Gene Knockout Promotes Podocyte Injury in Diabetic Mice

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2022 Jul 11

PMID 35813229

Authors

Rui Yan

Ye Zhang

Yuxing Yang

Lingling Liu

Lirong Liu

Ziwei Guo

Haiyan Yu

Yuanyuan Wang

Bing Guo

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effects of peroxisome proliferator-activated receptor (PPAR) expression on renal podocyte in diabetic mice by conditionally knockout mouse PPAR gene.

Methods: Wild-type C57BL mice and PPAR gene knockout mice were used as research objects to establish the diabetic mouse model, which was divided into normal control group (NC group), normal glucose PPAR gene knockout group (NK group), diabetic wild-type group (DM group), and diabetic PPAR gene knockout group (DK group), with 8 mice in each group. After 16 weeks, the mice were sacrificed for renal tissue collection. Morphological changes of renal tissue were observed by HE and Masson staining, and ultrastructure of renal tissue was observed by transmission electron microscope. Protein expressions of PPAR, podocin, nephrin, collagen IV, and fibronectin (FN) in renal tissues were detected by immunohistochemistry and Western blot, and mRNA changes of PPAR, podocin, and nephrin in renal tissues were detected by qRT-PCR.

Results: Compared with the NC group, the protein and mRNA expressions of PPAR, podocin, and nephrin decreased in the kidney tissue of mice in the DM group, while the protein expressions of collagen IV and FN increased. The expression of various proteins in kidney tissues of the DK group was consistent with that of the DM group, and the difference was more obvious. The expression of PPAR protein and mRNA decreased in the NK group, while the expression of podocin, nephrin protein and mRNA, collagen IV, and FN protein showed no significant difference.

Conclusion: In diabetic renal tissue, the loss of PPAR can aggravate podocellular damage and thus promote the occurrence of diabetic renal fibrosis. Increasing the expression of PPAR may effectively relieve renal podocyte impairment in diabetic patients, which can be used for the treatment of diabetic nephropathy.

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