CD146⁺ Endothelial Cells Facilitate Renal Interstitial Fibrosis Through Endothelial-to-Mesenchymal Transition.

Abstract

BACKGROUND Endothelial cells play a crucial role in the pathogenesis of renal interstitial fibrosis (RIF), with CD146 being upregulated on injured endothelial cells. However, the precise contribution of CD146⁺ endothelial cells to RIF remains unclear. This study aimed to observe and detect the relationship between CD146 expression and endothelial cells and to explore the role and possible mechanism of CD146 promoting endothelial-mesenchymal transition in RIF. MATERIAL AND METHODS In this study, we investigated the association between CD146⁺ endothelial cells and RIF. Double-label immunofluorescence was used in patients with chronic kidney disease, whereas multiplex immunofluorescence staining was used for the analysis in unilateral ureteral obstruction (UUO) mice. Hematoxylin and eosin and Masson trichrome staining were performed to evaluate RIF. RESULTS Our results revealed an elevation of CD146⁺ endothelial cells, which positively correlated with the degree of RIF in chronic kidney disease patients and UUO mice. Notably, CD146⁺ endothelial cells undergoing endothelial-mesenchymal transition (CD146⁺ EndMT) were significantly higher in subjects with severe renal interstitial fibrosis, as observed in chronic kidney disease patients and UUO mice. Additionally, with the progression of renal interstitial fibrosis, the expression of PDGFRb, the receptor of PDGF-B signaling pathway, increased and co-localized with CD146⁺ CD31⁺ a-SMA⁺ cells. The proportion of CD146⁺ CD31⁺ alpha-SMA⁺ PDGFRß⁺ cells in CD31⁺ cells increased. CONCLUSIONS In the process of renal interstitial fibrosis, CD146 is mainly expressed in renal interstitial vascular endothelial cells and participates in endothelial-to-mesenchymal transition, which may be related to the PDGF-B/PDGFR-ß signaling pathway.