Knockdown of CD146 promotes endothelial-to-mesenchymal transition via Wnt/β-catenin pathway.

PLoS One

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Published: August 2022

Purpose: Cardiac fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) proteins and leads to the maladaptive changes in myocardium. Endothelial cells (ECs) undergoing mesenchymal transition contributes to the occurrence and development of cardiac fibrosis. CD146 is an adhesion molecule highly expressed in ECs. The present study was performed to explore the role of CD146 in modulating endothelial to mesenchymal transition (EndMT).

Methods: C57BL/6 mice were subjected to subcutaneous implantation of osmotic minipump infused with angiotensin II (Ang Ⅱ). Adenovirus carrying CD146 short hairpin RNA (shRNA) or CD146 encoding sequence were infected into cultured human umbilical vein endothelial cells (HUVECs) followed by stimulation with Ang II or transforming growth factor-β1 (TGF-β1). Differentially expressed genes were revealed by RNA-sequencing (RNA-Seq) analysis. Gene expression was measured by quantitative real-time PCR, and protein expression and distribution were determined by Western blot and immunofluorescence staining, respectively.

Results: CD146 was predominantly expressed by ECs in normal mouse hearts. CD146 was upregulated in ECs but not fibroblasts and myocytes in hearts of Ang II-infused mice and in HUVECs stimulated with Ang Ⅱ. RNA-Seq analysis revealed the differentially expressed genes related to EndMT and Wnt/β-catenin signaling pathway. CD146 knockdown and overexpression facilitated and attenuated, respectively, EndMT induced by Ang II or TGF-β1. CD146 knockdown upregulated Wnt pathway-related genes including Wnt4, LEF1, HNF4A, FOXA1, SOX6, and CCND3, and increased the protein level and nuclear translocation of β-catenin.

Conclusions: Knockdown of CD146 exerts promotional effects on EndMT via activating Wnt/β-catenin pathway and the upregulation of CD146 might play a protective role against EndMT and cardiac fibrosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401105PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0273542PLOS

Publication Analysis

Top Keywords

cardiac fibrosis
12
cd146
10
knockdown cd146
8
wnt/β-catenin pathway
8
endothelial cells
8
mesenchymal transition
8
expressed ecs
8
ang Ⅱ
8
differentially expressed
8
expressed genes
8

Similar Publications

The influence of the mitochondrial control system on ischemic heart disease has become a major focus of current research. Mitophagy, as a very crucial part of the mitochondrial control system, plays a special role in ischemic heart disease, unlike mitochondrial dynamics. The published reviews have not explored in detail the unique function of mitophagy in ischemic heart disease, therefore, the aim of this paper is to summarize how mitophagy regulates the progression of ischemic heart disease.

View Article and Find Full Text PDF

Objective: Macrophages perform vital functions in cardiac remodeling after myocardial infarction (MI). Transglutaminase 2 (TG2) participates in fibrosis. Nevertheless, the role of TG2 in MI and mechanisms underlying macrophage polarization are unclear.

View Article and Find Full Text PDF

OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1.

BMC Cardiovasc Disord

December 2024

Department of General Medicine, The Affiliated Hospital of Inner Mongolia Medical University, No.1, Tongdao North Road, Huimin District, Hohhot, Inner Mongolia, 010050, China.

Background: Heart failure (HF) is a syndrome with complex etiology and high mortality in the world. Macrophage-related inflammation is involved in HF development. O-GlcNAcylation is a post-translational modification that affects pathological processes.

View Article and Find Full Text PDF

Background: Qi Li Qiang Xin (QLQX) capsule has a solid theoretical basis and clinical efficacy in the treatment of chronic heart failure; however, the underlying mechanisms remain obscure. This study was designed to determine the effect of the QLQX on the treatment of heart failure and delineate the underlying mechanisms via a nontargeted metabolomics and lipidomics approach.

Methods: A rat model of heart failure after myocardial infarction (MI) was established via permanent ligation of the anterior descending branch of the left coronary artery.

View Article and Find Full Text PDF

VPO1 Promotes Programmed Necrosis of Cardiomyocytes in Rats with Chronic Heart Failure by Upregulating CYLD.

Front Biosci (Landmark Ed)

December 2024

Department of Cardiovascular Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, 410008 Changsha, Hunan, China.

Background: Chronic heart failure (CHF) is a serious cardiovascular condition. Vascular peroxidase 1 (VPO1) is associated with various cardiovascular diseases, yet its role in CHF remains unclear. This research aims to explore the involvement of VPO1 in CHF.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!