Putative endothelial progenitor cells do not promote vascular repair but attenuate pericyte-myofibroblast transition in UUO-induced renal fibrosis

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Abstract

Background: Putative endothelial progenitor cells (pEPCs) have been confirmed to participate in alleviation of renal fibrosis in several ischaemic diseases. However, their mechanistic effect on renal fibrosis, which is characterized by vascular regression and further rarefaction-related pathology, remains unknown. Methods: To explore the effect and molecular mechanisms by which pEPCs act on unilateral ureteral obstruction (UUO)-induced renal fibrosis, we isolated pEPCs from murine bone marrow. In vivo, pEPCs (2 × 10 5 cells/day) and pEPC-MVs (microvesicles) were injected into UUO mice via the tail vein. In vitro, pEPCs were co-cultured with renal-derived pericytes. Pericyte-myofibroblast transition was evaluated using the myofibroblast marker α-smooth muscle actin (α-SMA) and pericyte marker platelet-derived growth factor receptor β (PDGFR-β). Results: Exogenous supply of bone marrow-derived pEPCs attenuated renal fibrosis by decreasing pericyte-myofibroblast transition without significant vascular repair in the UUO model. Our results indicated that pEPCs regulated pericytes and their transition into myofibroblasts via pEPC-MVs. Co-culture of pericytes with pEPCs in vitro suggested that pEPCs inhibit transforming growth factor-β (TGF-β)-induced pericyte-myofibroblast transition via a paracrine pathway. Conclusion: pEPCs effectively attenuated UUO-induced renal fibrosis by inhibiting pericyte-myofibroblast transition via a paracrine pathway, without promoting vascular repair.

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Yang, J., Wang, M., Zhu, F., Sun, J., Xu, H., Chong Lee Shin, O. L. S., … Yao, Y. (2019). Putative endothelial progenitor cells do not promote vascular repair but attenuate pericyte-myofibroblast transition in UUO-induced renal fibrosis. Stem Cell Research and Therapy, 10(1). https://doi.org/10.1186/s13287-019-1201-5

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