Propofol ameliorates renal ischemia/reperfusion injury by enhancing macrophage M2 polarization through PPARγ/STAT3 signaling.

Abstract

Propofol (Pro) confers protection against renal ischemia/reperfusion (rI/R) injury through incompletely characterized mechanisms. Since Pro has shown net anti-inflammatory properties as part of its beneficial effects, we examined the potential role of Pro in the modulation of macrophage polarization status during both rI/R injury in vivo and exposure of cultured peritoneal macrophages (PMs) to hypoxia/reoxygenation (H/R). Rats were subjected to 45-min r/IR surgery or a sham procedure and administered PBS (vehicle) or Pro during the ischemia stage. Pro administration attenuated rI/R-induced kidney damage and renal TNF-α, IL-6, and CXCL-10 expression. Enhanced macrophage M2 polarization, evidenced by reduced iNOS and increased Arg1 and Mrc1 mRNA levels, was further detected after Pro treatment both in the kidney, after rI/R in vivo, and in H/R-treated PMs. Pro administration also repressed phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and increased p-STAT3, p-STAT6, and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA levels in H/R-exposed PMs. Importantly, siRNA-mediated PPARγ silencing repressed Pro-mediated STAT3 activation in PMs and restored proinflammatory cytokine levels and prevented macrophage M2 marker expression in both rI/R-treated rats and cultured PMs. These findings suggest that Pro confers renoprotection against rI/R by stimulating PPARγ/STAT3-dependent macrophage conversion to the M2 phenotype.

• Authors: Zhaohui Liu, Yanli Meng, Yu Miao, Lili Yu, Qianjie Wei, Yuqing Li, Bing Zhang, Qiannan Yu
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 11 Pg. 15511-15522 (06 10 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 34111028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PPAR gamma
• Protective Agents
• STAT3 Transcription Factor
• Propofol

Topics

• Animals
• Cell Polarity (drug effects)
• Gene Silencing (drug effects)
• Inflammation (pathology)
• Kidney (pathology)
• Macrophages (drug effects, metabolism, pathology)
• Male
• PPAR gamma (metabolism)
• Propofol (pharmacology, therapeutic use)
• Protective Agents (pharmacology)
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, pathology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction