Emerging roles of inflammation-mediated endothelial–mesenchymal transition in health and disease

Abstract

Endothelial–mesenchymal transition (EndoMT), a cellular differentiation process in which endothelial cells (ECs) lose their properties and differentiate into mesenchymal cells, has been observed not only during development but also in various pathological states in adults, including cancer progression and organ/tissue fibrosis. Transforming growth factor-β (TGF-β), an inflammation-related cytokine, has been shown to play central roles in the induction of EndoMT. TGF-β induces EndoMT by regulating the expression of various transcription factors, signaling molecules, and cellular components that confer ECs with mesenchymal characteristics. However, TGF-β by itself is not necessarily sufficient to induce EndoMT to promote the progression of EndoMT-related diseases to a refractory extent. In addition to TGF-β, additional activation by other inflammatory factors is often required to stabilize the progression of EndoMT. Since recent lines of evidence indicate that inflammatory signaling molecules act as enhancers of EndoMT, we summarize the roles of inflammatory factors in the induction of EndoMT and related diseases. We hope that this review will help to develop therapeutic strategies for EndoMT-related diseases by targeting inflammation-mediated EndoMT.

Investigation of Anti-Epithelial-Mesenchymal Transition and Anti-Inflammation effects of Qing Fei Hua Xian Decotion on Pulmonary Fibrosis via Network Pharmacology and Experimental Verification

“…Our study also found that the expressions of TNF-α, IL-6, IL-1β and MPO level were increased in BLM-treated rats, in accordance with other studies using the same animal model [34]. It is widely accepted that in ammation response contributes to the development of EMT, which plays a crucial role in driving the PF development [51,52]. It has been reported that TNF-α induced EMT was through activation of Akt/NF-κB (nuclear factor kappa B) pathway in a renal allograft interstitial brosis [53].…”

Comprehensive characterization of the transcriptional response to COVID-19 in multiple organs reveals shared signatures across tissues

“…Wang et al 2019). Finally, TGFβ signaling is linked to the response of endothelial cells to inflammation in COVID-19 (Yoshimatsu and Watabe 2022). Together, these results build on previously reported evidence to show that multiple signaling pathways in the heart undergo both cell type-specific and systemic changes in response to COVID-19.…”

The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

“…It was shown that activated FGFR1 recruits FRS2α, which induces let-7 microRNA expression and suppresses the expression of TGFβRI [ 89 , 90 ]. However, inflammatory cytokines, including TNF-α, IFN, and IL-1β, inhibit FGFR1 signaling and enhance EndoMT in some cultured endothelial cells [ 91 ].…”

“…Extensive research has been conducted to elucidate the occurrence of EndoMT in in vitro studies. EndoMT is defined in these studies as cells that exhibit the following characteristics: (1) loss of endothelial properties, (2) coexpression of endothelial and mesenchymal markers, (3) increased migration, and (4) increased mesenchymal and myofibroblastic cells [ 23 , 91 ]. For example, Krenning et al demonstrated that when human umbilical cord endothelial cells (HUVECs) were passaged and cultured with TGF-β1 and PDGF-BB, these cells lost their endothelial markers and developed spindly shapes while gaining the capacity to produce a variety of fibroblast-specific molecules.…”

“…The EndoMT process has also been implicated in the embryonic development of multiple other vascular tissues, such as the formation of the abdominal aorta and the cardiac and semilunar valve [ 112 ]. Various stimuli, endothelin-1, angiotensin II, glucose, advanced glycation end-products, and inflammatory stimuli such as inflammatory mediators, growth factors, hypoxia, and proteases, can induce EndoMT via TGF-β signaling, which plays a vital role during the development of cardiovascular diseases [ 91 , 115 , 116 , 117 , 118 , 119 , 120 ].…”