scholarly journals Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition

2019 ◽  
Vol 15 (11) ◽  
pp. 2393-2407 ◽  
Author(s):  
Xiaolin Zheng ◽  
Meng Peng ◽  
Yan Li ◽  
Xule Wang ◽  
Wenjie Lu ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Cardiac Fibrosis ◽  
Diabetic Mice ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

scholarly journals A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse

2020 ◽  
Vol 127 (3) ◽  
Author(s):  
Jaime Ibarrola ◽  
Amaia Garcia-Peña ◽  
Lara Matilla ◽  
Benjamin Bonnard ◽  
Rafael Sádaba ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Mineralocorticoid Receptor ◽  
Cell Activation ◽  
Cardiac Fibrosis ◽  
Interstitial Cell ◽  
Activation Markers ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

Rationale: Mitral valve prolapse (MVP) is one of the most common valvular disorders. However, the molecular and cellular mechanisms involved in fibromyxomatous changes in the mitral leaflet tissue have not been elucidated. Aldosterone (Aldo) promotes fibrosis in myocardium, and MR (mineralocorticoid receptor) antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis. Objective: We investigated the role of the Aldo/MR in the fibromyxomatous modifications associated with MVP. Methods and Results: Aldo enhanced valvular interstitial cell activation markers and induced endothelial-mesenchymal transition in valvular endothelial cells, resulting in increased proteoglycan secretion. MRA blocked all the above effects. Cytokine arrays showed CT-1 (cardiotrophin-1) to be a mediator of Aldo-induced valvular interstitial cell activation and proteoglycan secretion and CD (cluster of differentiation) 14 to be a mediator of Aldo-induced endothelial-mesenchymal transition and proteoglycan secretion in valvular endothelial cells. In an experimental mouse model of MVP generated by nordexfenfluramine administration, MRA treatment reduced mitral valve thickness and proteoglycan content. Endothelial-specific MR deletion prevented fibromyxomatous changes induced by nordexfenfluramine administration. Moreover, proteoglycan expression was slightly lower in the mitral valves of MVP patients treated with MRA. Conclusions: These findings demonstrate, for the first time, that the Aldo/MR pathway regulates the phenotypic, molecular, and histological changes of valvular interstitial cells and valvular endothelial cells associated with MVP development. MRA treatment appears to be a promising option to reduce fibromyxomatous alterations in MVP.

scholarly journals Dual roles of chromatin remodeling protein BRG1 in angiotensin II-induced endothelial–mesenchymal transition

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Zilong Li ◽  
Xiaochen Kong ◽  
Yuanyuan Zhang ◽  
Yangxi Zhang ◽  
Liming Yu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Chromatin Remodeling ◽  
Cardiac Fibrosis ◽  
Vascular Endothelial Cells ◽  
Epigenetic Mechanism ◽  
Ang Ii ◽  
Dual Roles ◽  
Mesenchymal Transition ◽  
The One ◽  
Endothelial Mesenchymal Transition

Abstract Endothelial–mesenchymal transition (EndMT) is considered one of the processes underlying tissue fibrosis by contributing to the pool of myofibroblasts. In the present study, we investigated the epigenetic mechanism whereby angiotensin II (Ang II) regulates EndMT to promote cardiac fibrosis focusing on the role of chromatin remodeling protein BRG1. BRG1 knockdown or inhibition attenuated Ang II-induced EndMT, as evidenced by down-regulation of CDH5, an endothelial marker, and up-regulation of COL1A2, a mesenchymal marker, in cultured vascular endothelial cells. On the one hand, BRG1 interacted with and was recruited by Sp1 to the SNAI2 (encoding SLUG) promoter to activate SNAI2 transcription in response to Ang II stimulation. Once activated, SLUG bound to the CDH5 promoter to repress CDH5 transcription. On the other hand, BRG1 interacted with and was recruited by SRF to the COL1A2 promoter to activate COL1A2 transcription. Mechanistically, BRG1 evicted histones from the target promoters to facilitate the bindings of Sp1 and SRF. Finally, endothelial conditional BRG1 knockout mice (CKO) exhibited a reduction in cardiac fibrosis, compared to the wild type (WT) littermates, in response to chronic Ang II infusion. In conclusion, our data demonstrate that BRG1 is a key transcriptional coordinator programming Ang II-induced EndMT to contribute to cardiac fibrosis.

scholarly journals 166 HDAC3 Unconventional Splicing Mediates Endothelial-Mesenchymal Transition in Cardiac Fibrosis

Heart ◽  
2016 ◽  
Vol 102 (Suppl 6) ◽  
pp. A117.1-A117
Author(s):  
Ka Hou Lao ◽  
Dario Ummarino ◽  
Ajay Shah ◽  
Lingfang Zeng
Keyword(s):  
Cardiac Fibrosis ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition ◽  
Unconventional Splicing

scholarly journals Hepatocyte Growth Factor Reduces Cardiac Fibrosis by Inhibiting Endothelial-Mesenchymal Transition

Hypertension ◽  
2012 ◽  
Vol 59 (5) ◽  
pp. 958-965 ◽  
Author(s):  
Keita Okayama ◽  
Junya Azuma ◽  
Norio Dosaka ◽  
Kazuma Iekushi ◽  
Fumihiro Sanada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cardiac Fibrosis ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth ◽  
Endothelial Mesenchymal Transition

scholarly journals Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT

2020 ◽  
Vol 11 ◽  
Author(s):  
Sen Shi ◽  
Li Song ◽  
Hao Yu ◽  
Songlin Feng ◽  
Jianhua He ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Diabetic Mice ◽  
Diabetic Kidney ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Non Coding Rnas ◽  
Endothelial Mesenchymal Transition

Diabetic nephropathy is the leading cause of kidney fibrosis. Recently, altered expressed or dysfunction of some long non-coding RNAs (lncRNAs) has been linked to kidney fibrosis; however, the mechanisms of lncRNAs in kidney fibrosis remain unclear. We have shown that the DPP-4 inhibitor linagliptin can inhibit endothelial-mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with DPP-4 protein levels via the induction of miR-29. Here, we found that expression of the lncRNA H19 was significantly up-regulated in TGF-β2-induced fibrosis in human dermal microvascular endothelial cells (HMVECs) in vitro, and in kidney fibrosis of streptozotocin-induced diabetic CD-1 mice. We also detected up-regulated H19 expression and down-regulated miR-29a expression in the early and advanced mouse models of diabetic kidney fibrosis. H19 knockdown significantly attenuated kidney fibrosis in vitro and in vivo, which was associated with the inhibition of the EndMT-associated gene FSP-1. We also found that the up-regulation of H19 observed in fibrotic kidneys associated with the suppression of miR-29a in diabetic mice. H19, miR-29a, and EndMT contribute to a regulatory network involved in kidney fibrosis, and are associated with regulation of the TGF-β/SMAD3 singling pathway. This study indicates that inhibition of LncRNA H19 represents a novel anti-fibrotic treatment for diabetic kidney diseases.

Sign in / Sign up

Export Citation Format

Share Document