T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration

Chen, Lian-Di; Zhu, Wenting; Cheng, Yuanyuan; Li, Zhenhua; Chen, Yiqing; Yuan, Zhongwen; Lin, Cai-Yan; Jing, Dong-Dong; Liu, Zhongqiu; Yan, Pengke

doi:10.1016/j.atherosclerosis.2020.01.017

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…However, one should also take into consideration that these receptors also play important roles in other cell types involved in inflammatory processes (and associated events) like epithelial cells, fibroblasts, and smooth muscle cells [77,90,111,137]. For example, OGR1 has been shown to play a role in endoplasmic reticulum stress in an epithelial cell line [77], inhibition of GPR4 in fibroblasts reduces pHdependent transition to myofibroblasts [137], and TDAG8 participates in proliferation and migration of smooth muscle cells with impact in atherosclerosis [11].…”

Section: A Brief Overview On the Role Of Proton-activated Gpcrs In Or...mentioning

confidence: 99%

Physiological relevance of proton-activated GPCRs

Silva

Wagner

2022

Pflugers Arch - Eur J Physiol

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The detection of H+ concentration variations in the extracellular milieu is accomplished by a series of specialized and non-specialized pH-sensing mechanisms. The proton-activated G protein–coupled receptors (GPCRs) GPR4 (Gpr4), TDAG8 (Gpr65), and OGR1 (Gpr68) form a subfamily of proteins capable of triggering intracellular signaling in response to alterations in extracellular pH around physiological values, i.e., in the range between pH 7.5 and 6.5. Expression of these receptors is widespread for GPR4 and OGR1 with particularly high levels in endothelial cells and vascular smooth muscle cells, respectively, while expression of TDAG8 appears to be more restricted to the immune compartment. These receptors have been linked to several well-studied pH-dependent physiological activities including central control of respiration, renal adaption to changes in acid–base status, secretion of insulin and peripheral responsiveness to insulin, mechanosensation, and cellular chemotaxis. Their role in pathological processes such as the genesis and progression of several inflammatory diseases (asthma, inflammatory bowel disease), and tumor cell metabolism and invasiveness, is increasingly receiving more attention and makes these receptors novel and interesting targets for therapy. In this review, we cover the role of these receptors in physiological processes and will briefly discuss some implications for disease processes.

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Section: A Brief Overview On the Role Of Proton-activated Gpcrs In Or...mentioning

confidence: 99%

Physiological relevance of proton-activated GPCRs

Silva

Wagner

2022

Pflugers Arch - Eur J Physiol

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“…Regarding a link between TDAG8 and the cholesterol biosynthesis pathway, there is a report that TDAG8 accelerates cholesterol accumulation in an atherosclerotic mouse model via proliferation and migration in vascular smooth muscle cells [ 36 ]. In addition, TDAG8-deficient mice show reduced cholesterol metabolism in T helper cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder

et al. 2023

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Few studies report the microglia involvement in the pathogenesis of panic disorder (PD), although the crucial role of microglia in other neuropsychiatric diseases is being emphasized. In addition, there is no report to characterize the phenotypic and functional levels of PD patient-derived microglia to find their clinical relevance. Herein, we used a model to induce patient-derived microglia-like cells (iMGs) to clarify the molecular characteristics and function of PD-iMGs. We established iMGs from 17 PD patients and 16 healthy controls (non-psychiatric controls, HC). PD-iMGs showed increased T-cell death-associated gene-8 expression per the proposal of a previous in vivo study. In addition, we found that patient-derived iMGs showed reduced phagocytosis and increased TREM2 expression. We analyzed the phenotype of the PD-iMGs by RNA sequencing. The PD-iMGs clustered together distinct from HC-iMGs. Gene set enrichment analysis revealed the involvement of cholesterol biosynthesis and steroid metabolism in PD-iMGs. Regarding the cholesterol synthesis pathway, we discovered ACAT2 and DHCR7 as the most impacted genes related to a character of PD-iMGs compared to HC-iMGs. The ACAT2, a major cholesterol esterifier, was increased in PD-iMGs. Nevertheless, PD-iMGs did not show lipid droplet accumulation. Interestingly, ACAT2 expression was inversely correlated with the severity of depression and anxiety sensitivity to publicly observable anxiety reactions. We propose that microglia of PD patients have unique characteristics with dysregulation of cholesterol biosynthesis pathway and impaired phagocytosis, reflecting clinical phenotype.

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“…On the other hand, CHK1 and CHK2 inhibit CDC2 by inactivating the phosphatase CDC25 24 . It is well known that contractile VSMCs have weak, while synthetic VSMCs have enhanced proliferative and migratory abilities 36 . METTL3 inhibited the proliferation of VSMCs, implying a phenotypic switching.…”

Section: Discussionmentioning

confidence: 99%

Methyltransferase‐like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation

et al. 2022

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Prevention of neointima formation is the key to improving long-term outcomes after stenting or coronary artery bypass grafting. RNA N 6 -methyladenosine (m 6 A) methylation has been reported to be involved in the development of various cardiovascular diseases, but whether it has a regulatory effect on neointima formation is unknown.Herein, we revealed that methyltransferase-like 3 (METTL3), the major methyltrans-

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T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration

Cited by 14 publications

References 24 publications

Physiological relevance of proton-activated GPCRs

Physiological relevance of proton-activated GPCRs

A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder

Methyltransferase‐like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation

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