Microvesicles derived from human umbilical cord mesenchyme promote M2 macrophage polarization and ameliorate renal fibrosis following partial nephrectomy via hepatocyte growth factor

Abstract

The intraoperative ischemia in partial nephrectomy (PN) often leads to postoperative renal function impairment and fibrosis, which can be regulated by macrophage polarization. We have previously demonstrated that microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells (hWJMSC-MVs) attenuated renal ischemia-induced renal fibrosis and contained a substantial quantity of hepatocyte growth factor (HGF). Herein, we investigated whether MSC-MVs regulate macrophage polarization and ameliorate renal fibrosis following ischemia-PN via transferring HGF. A rat model of ischemia-PN was established by 45 min of left renal ischemia followed by removal of 1/3 upper left kidney. MSC-MVs were injected through the tail vein immediately after ischemia. Renal injury biomarkers were measured and histologic analysis was performed to analyze renal injury. A co-culture model of THP-1 macrophages and MSC-MVs was utilized. The expression of M1 markers and M2 markers were determined to evaluate macrophage polarization. MSC-MV administration significantly ameliorated renal inflammation, lesions, and fibrosis in ischemia-PN rats, and promoted M2 macrophage polarization both in rat remnant renal tissues and LPS-treated THP-1 cells. These effects of MSC-MVs were compromised when HGF expression was downregulated in MSC-MVs. Collectively, MSC-MVs promote M2 macrophage polarization and attenuate renal fibrosis following ischemia-PN via transferring HGF.

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Funding

This study was supported by grants from 23456 Talent Project of Henan Provincial People’s Hospital [No. ZC23456005]; Henan Province Medical Science and Technology Research Plan.

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TD, GJ, JZ, LR, and TJ performed the experiments; XZ and RZ analyzed the data; WC and LZ interpreted the data; TD drafted the manuscript; TD and DD designed the project and reviewed the manuscript. All the authors gave final approval of the version to be published.

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Correspondence to Degang Ding or Tongyu Ji.

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This study was approved by the Ethics Committee of Zhengzhou University People’s Hospital.

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Du, T., Ju, G., Zhou, J. et al. Microvesicles derived from human umbilical cord mesenchyme promote M2 macrophage polarization and ameliorate renal fibrosis following partial nephrectomy via hepatocyte growth factor. Human Cell (2021). https://doi.org/10.1007/s13577-021-00525-z

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Keywords

  • Micro-vesicles
  • Hepatocyte growth factor
  • Macrophage
  • Partial nephrectomy
  • Fibrosis