Putative endothelial progenitor cells do not promote vascular repair but attenuate pericyte-myofibroblast transition in UUO-induced renal fibrosis.
Stem Cell Res Ther
; 10(1): 104, 2019 03 21.
Article
em En
| MEDLINE
| ID: mdl-30898157
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 × 105 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 ß (PDGFR-ß).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-ß (TGF-ß)-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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Obstrução Ureteral
/
Células da Medula Óssea
/
Comunicação Parácrina
/
Pericitos
/
Miofibroblastos
/
Células Progenitoras Endoteliais
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China