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

• Published in: Stem cell research & therapy Vol. 10; no. 1; p. 104
• Main Authors: Yang, Juan, Wang, Meng, Zhu, Fengming, Sun, Jie, Xu, Huzi, Chong Lee Shin, Octavia Li-Sien, Zhao, Zhi, Pei, Guangchang, Zhu, Han, Cao, Chujin, He, Xiaofeng, Huang, Yi, Ma, Zufu, Liu, Liu, Wang, Le, Ning, Yong, Liu, Wei, Xu, Gang, Wang, Xiaohui, Zeng, Rui, Yao, Ying
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.03.2019; BioMed Central; BMC
• Subjects: Actin; Angiogenesis; Animals; Blood cells; Bone marrow; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Bone morphogenetic proteins; Cell culture; Complications and side effects; Endothelial Progenitor Cells - metabolism; Endothelial Progenitor Cells - pathology; Endothelial Progenitor Cells - transplantation; Endothelium; Fibrosis; Growth factors; Kidney diseases; Kidney Diseases - etiology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Diseases - therapy; Kidneys; Laboratory animals; Male; Mice; Mice, Transgenic; MicroRNAs; Microvesicles; Molecular modelling; Muscle proteins; Myofibroblasts - metabolism; Myofibroblasts - pathology; Paracrine Communication; Paracrine signalling; Pericytes; Pericytes - metabolism; Pericytes - pathology; Pericyte–myofibroblast transition; Platelet-derived growth factor; Progenitor cells; Putative endothelial progenitor cells; Renal fibrosis; Risk factors; Smooth muscle; Stem cells; Surgery; Transforming growth factor; Transforming growth factor-b; Transforming growth factors; Ureteral obstruction; Ureteral Obstruction - complications; Ureteral Obstruction - metabolism; Ureteral Obstruction - pathology; Ureteral Obstruction - therapy; Beijing China; United States > US; China; Putative endothelial progenitor cells; Pericyte–myofibroblast transition; Microvesicles; Renal fibrosis
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-019-1201-5

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. 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 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). 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. pEPCs effectively attenuated UUO-induced renal fibrosis by inhibiting pericyte-myofibroblast transition via a paracrine pathway, without promoting vascular repair.