EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Published on May 19, 2021in Frontiers in Cell and Developmental Biology5.201
· DOI :10.3389/FCELL.2021.683594
Roberta Giordo13
Estimated H-index: 13
(College of Health Sciences, Bahrain),
Yusra M. A. Ahmed (College of Health Sciences, Bahrain)+ 5 AuthorsGianfranco Pintus32
Estimated H-index: 32
(University of Sassari)
Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.
Diabetic retinopathy (DR) is one of the serious complications that occurs in diabetic patients that frequently causes blindness. Long noncoding RNAs (lncRNAs) have been associated with DR pathology...
1 CitationsSource
#1Laongthip Ruknarong (KKU: Khon Kaen University)H-Index: 1
#2Chongchira Boonthongkaew (KKU: Khon Kaen University)H-Index: 2
Last. Chanvit Leelayuwat (KKU: Khon Kaen University)H-Index: 16
view all 8 authors...
Background Vitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease. Methods Pre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) fu...
#1Roberta Giordo (College of Health Sciences, Bahrain)H-Index: 13
#2Gheyath K. Nasrallah (College of Health Sciences, Bahrain)H-Index: 26
Last. Gianfranco Pintus (College of Health Sciences, Bahrain)H-Index: 32
view all 7 authors...
Diabetes-associated long-term hyperglycaemia leads to oxidative stress-mediated fibrosis in different tissues and organs. Endothelial-to-mesenchymal-transition (EndMT) appears to play a role in diabetes-associated fibrotic conditions. Here, we investigate whether EndMT is implicated in the diabetic retinopathy fibrotic process and evaluate the possibility that resveratrol could counteract EndMT by inhibiting high glucose (HG)-induced increases in ROS. Primary Human Retinal Endothelial Cells (HRE...
#1Dan Chen (CQMU: Chongqing Medical University)H-Index: 6
#2Cheng Zhang (CQMU: Chongqing Medical University)H-Index: 10
Last. Qingzhong Xiao (Guangzhou Medical University)H-Index: 41
view all 13 authors...
Increasing evidence has suggested a critical role for endothelial-to-mesenchymal transition (EndoMT) in a variety of pathological conditions. MicroRNA-200c-3p (miR-200c-3p) has been implicated in epithelial-to-mesenchymal transition. However, the functional role of miR-200c-3p in EndoMT and neointimal hyperplasia in artery bypass grafts remains largely unknown. Here we demonstrated a critical role for miR-200c-3p in EndoMT. Proteomics and luciferase activity assays revealed that fermitin family ...
#1Xianxian Wu (Peking Union Medical College)H-Index: 2
#2Xingchen DuH-Index: 1
Last. Zhiwei Yang (Peking Union Medical College)H-Index: 16
view all 10 authors...
Abstract Aims Endothelial to mesenchymal transition (EndMT) is closely related to atherosclerosis. Herein, we aim to determine whether miR-122 is involved in EndMT and the underlying mechanism in atherosclerosis. Main methods qRT-PCR was performed to detect miR-122 expression in ApoE−/− mice and cellular EndMT model induced by H2O2. MiR-122 expression in vivo was modulated by lenti-virus injection and by genetic manipulation. Hematoxylin and eosin (HE) and Oil-red O staining were used to observe...
1 CitationsSource
#1Jia LiuH-Index: 1
#2Feng JiangH-Index: 1
Last. Zhuhong ZhangH-Index: 1
view all 9 authors...
Exosomes, nanoscale vesicles with a diameter of 30 to 150 nm, are composed of a lipid bilayer, protein, and genetic material. Exosomes are secreted by virtually all types of cells in the human body. They have key functions in cell-to-cell communication, immune regulation, inflammatory response, and neovascularization. Mounting evidence indicates that exosomes play an important role in various diseases, such as cancer, cardiovascular diseases, and brain diseases; however, the role that exosomes p...
#2Keizo Kanasaki (Shimane University)H-Index: 5
Last. Julie E. GoodwinH-Index: 13
view all 3 authors...
Disruption of mitochondrial biosynthesis or dynamics, or loss of control over mitochondrial regulation leads to a significant alteration in fuel preference and metabolic shifts that potentially affect the health of kidney cells. Mitochondria regulate metabolic networks which affect multiple cellular processes. Indeed, mitochondria have established themselves as therapeutic targets in several diseases. The importance of mitochondria in regulating the pathogenesis of several diseases has been reco...
1 CitationsSource
#1Sen ShiH-Index: 3
#2Li SongH-Index: 1
Last. Yanzheng HeH-Index: 11
view all 7 authors...
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 ...
2 CitationsSource
#1Jinpeng Li (Kanazawa Medical University)H-Index: 8
#2Haijie Liu (Kanazawa Medical University)H-Index: 2
Last. Keizo Kanasaki (Kanazawa Medical University)H-Index: 38
view all 10 authors...
Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis. We have reported that N-acetyl-seryl-aspartyl- lysyl-proline (AcSDKP) restored levels of diabetes m...
4 CitationsSource
#1Baoyan FanH-Index: 4
#2Michael ChoppH-Index: 161
Last. Xian Shuang LiuH-Index: 19
view all 4 authors...
Diabetic neuropathy (DN) is the most prevalent chronic complication of diabetes mellitus. The exact pathophysiological mechanisms of DN are unclear; however, communication network dysfunction among axons, Schwann cells, and the microvascular endothelium likely play an important role in the development of DN. Mounting evidence suggests that microRNAs (miRNAs) act as messengers that facilitate intercellular communication and may contribute to the pathogenesis of DN. Deregulation of miRNAs is among...
1 CitationsSource
Cited By0