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Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
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Protective effects of GPR120 agonist-programmed macrophages on renal interstitial fibrosis in unilateral ureteral

Li Wang1, Xu Ren1, Xue-Fei Tian2

  • 1Department of Nephrology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710005, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 2, 2019
PubMed

Insights

Programming macrophages with a GPR120 agonist effectively treats kidney fibrosis. This approach reprograms macrophages to an M2 phenotype, reducing inflammation and protecting against renal interstitial fibrosis (RIF).

Area of Science:

  • Nephrology
  • Immunology
  • Cell Biology

Background:

  • Macrophages exhibit diverse roles in renal interstitial fibrosis (RIF), with M2 phenotype macrophages offering protection.
  • Free fatty acid receptor GPR120 activation promotes M2 macrophage polarization.

Purpose of the Study:

  • To investigate the therapeutic potential of GPR120 agonist-programmed macrophages in treating RIF.

Main Methods:

  • Peritoneal macrophages from rats were incubated with the GPR120 agonist TUG891 in vitro.
  • Programmed macrophages were autologously transplanted into rats undergoing unilateral ureteral obstruction (UUO) to induce RIF.
  • RIF was assessed using histological staining, immunohistochemistry, and Western blot to analyze protein expression.

Main Results:

  • TUG891-programmed macrophages exhibited increased CD206 and arginase-1 expression, with decreased interleukin-6 and tumor necrosis factor-α.
  • Transplantation of programmed macrophages significantly alleviated RIF in UUO rats.
  • Programmed macrophages suppressed abnormal expression of TGF-β1, SMAD2, and epithelial-mesenchymal transition (EMT)-related proteins (vimentin, α-SMA, β-catenin).

Conclusions:

  • Autologous administration of GPR120 agonist-programmed macrophages demonstrates a protective effect against RIF.
  • This immunomodulatory strategy holds promise for RIF treatment by reprogramming macrophage phenotype.
Keywords:
GPR120MacrophageRenal interstitial fibrosisUnilateral ureteral obstruction

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