MicroRNA-155 Mediates Obesity-Induced Renal Inflammation and Dysfunction

Abstract

Chronic inflammation is a major contributor to obesity-related renal damage. Recent studies have demonstrated that microRNA (miR)-155 is closely associated with hyperglycemia-induced nephropathy, but whether renal miR-155 participates in the inflammatory response and development of obesity-related nephropathy is unknown. In present study, we investigated the pathophysiological role of renal miR-155 in palmitic acid (PA)-treated endothelial cell and high-fat-diet (HFD)-fed mouse models by specific miR-155 sponge. Mice fed with HFD exhibited higher levels of renal miR-155, which positively correlated with urine microalbumin and blood urea nitrogen. In vitro study, mouse renal vascular endothelial cells stimulated with PA also showed higher miR-155 levels, accompanied with increased inflammatory response. Suppression of renal miR-155 effectively attenuated HFD-induced renal structural damages and dysfunction. MiR-155 sponge treatment also significantly decreased NF-κB signaling and downstream gene expression in vitro and in vivo. The obesity-increased macrophage infiltration and lipotoxicity was decreased in mouse kidney after miR-155 sponge treatment. Mechanistically, miR-155 directly targeted 3′-UTR of SHIP1/INPP5D and suppressed its expression in vitro and in vivo, whereas silence of SHIP1/INPP5D abolished the renal protective benefits of miR-155 sponge in obese mice. Taken together, present findings for the first time provided evidence for the potential role of miR-155 in obesity-related nephropathy and clarified that SHIP1/NF-κB signaling was a potential molecular mechanism.

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Funding

This work was supported by Wenzhou Committee of Science and Technology of China (ZS2017008, Y20170055 and Y20180159), the Zhejiang Medical Science and Technology Research Fund Project of China (LY14H050006), the Guangdong Medical Science and Technology Research Fund Project of China (A2018042), the Guangzhou Science and Technology Project of China (20170420167), and Zhejiang Province Natural Science Foundation (LY16H150007).

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Correspondence to Chaosheng Chen or Ying Zhou.

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Zheng, C., Zhang, J., Chen, X. et al. MicroRNA-155 Mediates Obesity-Induced Renal Inflammation and Dysfunction. Inflammation 42, 994–1003 (2019). https://doi.org/10.1007/s10753-019-00961-y

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KEY WORDS

  • obesity
  • nephropathy
  • miR-155
  • inflammation
  • SHIP1/INPP5D