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Theranostics 2020; 10(26):12144-12157. doi:10.7150/thno.48562 This issue Cite

Research Paper

Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes

Meng Wang1*, Huzi Xu1*, Yinzheng Li1, Chujin Cao1, Han Zhu1, Yuxi Wang1, Zhi Zhao1, Guangchang Pei1, Fan Zhu1, Qian Yang1, Xuan Deng1, Cheng Zhou1, Yi Guo1, Jianliang Wu1, Wenhui Liao2, Juan Yang1✉, Ying Yao1,3✉, Rui Zeng1✉

1. Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.
2. Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.
3. Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.
*Meng Wang and Huzi Xu contributed equally to this work.

✉ Corresponding author: Rui Zeng1, E-mail: zengr126com; Ying Yao1,3, E-mail: yaoyingkkcom; Juan Yang1, E-mail: amy19861203com.

Citation:
Wang M, Xu H, Li Y, Cao C, Zhu H, Wang Y, Zhao Z, Pei G, Zhu F, Yang Q, Deng X, Zhou C, Guo Y, Wu J, Liao W, Yang J, Yao Y, Zeng R. Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes. Theranostics 2020; 10(26):12144-12157. doi:10.7150/thno.48562. https://www.thno.org/v10p12144.htm
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Abstract

Graphic abstract

Rationale: Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined.

Methods: We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis.

Results: Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes.

Conclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.

Keywords: PDGF-BB/PDGFR-β, pericyte, pEPCs, vascular injury, renal fibrosis.

Citation styles

APA
Wang, M., Xu, H., Li, Y., Cao, C., Zhu, H., Wang, Y., Zhao, Z., Pei, G., Zhu, F., Yang, Q., Deng, X., Zhou, C., Guo, Y., Wu, J., Liao, W., Yang, J., Yao, Y., Zeng, R. (2020). Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes. Theranostics, 10(26), 12144-12157. https://doi.org/10.7150/thno.48562.

ACS
Wang, M.; Xu, H.; Li, Y.; Cao, C.; Zhu, H.; Wang, Y.; Zhao, Z.; Pei, G.; Zhu, F.; Yang, Q.; Deng, X.; Zhou, C.; Guo, Y.; Wu, J.; Liao, W.; Yang, J.; Yao, Y.; Zeng, R. Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes. Theranostics 2020, 10 (26), 12144-12157. DOI: 10.7150/thno.48562.

NLM
Wang M, Xu H, Li Y, Cao C, Zhu H, Wang Y, Zhao Z, Pei G, Zhu F, Yang Q, Deng X, Zhou C, Guo Y, Wu J, Liao W, Yang J, Yao Y, Zeng R. Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes. Theranostics 2020; 10(26):12144-12157. doi:10.7150/thno.48562. https://www.thno.org/v10p12144.htm

CSE
Wang M, Xu H, Li Y, Cao C, Zhu H, Wang Y, Zhao Z, Pei G, Zhu F, Yang Q, Deng X, Zhou C, Guo Y, Wu J, Liao W, Yang J, Yao Y, Zeng R. 2020. Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes. Theranostics. 10(26):12144-12157.

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