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

Biomed Res Int. 2022 Jun 30:2022:9018379. doi: 10.1155/2022/9018379. eCollection 2022.

Abstract

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

Methods: Wild-type C57BL mice and PPARγ 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 PPARγ gene knockout group (NK group), diabetic wild-type group (DM group), and diabetic PPARγ 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 PPARγ, podocin, nephrin, collagen IV, and fibronectin (FN) in renal tissues were detected by immunohistochemistry and Western blot, and mRNA changes of PPARγ, podocin, and nephrin in renal tissues were detected by qRT-PCR.

Results: Compared with the NC group, the protein and mRNA expressions of PPARγ, 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 PPARγ 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 PPARγ can aggravate podocellular damage and thus promote the occurrence of diabetic renal fibrosis. Increasing the expression of PPARγ may effectively relieve renal podocyte impairment in diabetic patients, which can be used for the treatment of diabetic nephropathy.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Collagen Type IV / metabolism
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / metabolism
  • Gene Knockout Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Podocytes* / pathology
  • RNA, Messenger / metabolism

Substances

  • Collagen Type IV
  • PPAR gamma
  • Pparg protein, mouse
  • RNA, Messenger