Liu 2022 Adv Sci (Weinh)
Liu H, Liu Y, Wang H, Zhao Q, Zhang T, Xie SA, Liu Y, Tang Y, Peng Q, Pang W, Yao W, Zhou J (2022) Geometric constraints regulate energy metabolism and cellular contractility in vascular smooth muscle cells by coordinating mitochondrial DNA methylation. https://doi.org/10.1002/advs.202203995 |
Β» Adv Sci (Weinh) 9:e2203995. PMID: 36106364 Open Access
Liu Han, Liu Yuefeng, Wang He, Zhao Qiang, Zhang Tao, Xie Si-An, Liu Yueqi, Tang Yuanjun, Peng Qin, Pang Wei, Yao Weijuan, Zhou Jing (2022) Adv Sci (Weinh)
Abstract: Vascular smooth muscle cells (SMCs) can adapt to changes in cellular geometric cues; however, the underlying mechanisms remain elusive. Using 2D micropatterned substrates to engineer cell geometry, it is found that in comparison with an elongated geometry, a square-shaped geometry causes the nuclear-to-cytoplasmic redistribution of DNA methyltransferase 1 (DNMT1), hypermethylation of mitochondrial DNA (mtDNA), repression of mtDNA gene transcription, and impairment of mitochondrial function. Using irregularly arranged versus circumferentially aligned vascular grafts to control cell geometry in 3D growth, it is demonstrated that cell geometry, mtDNA methylation, and vessel contractility are closely related. DNMT1 redistribution is found to be dependent on the phosphoinositide 3-kinase and protein kinase B (AKT) signaling pathways. Cell elongation activates cytosolic phospholipase A2, a nuclear mechanosensor that, when inhibited, hinders AKT phosphorylation, DNMT1 nuclear accumulation, and energy production. The findings of this study provide insights into the effects of cell geometry on SMC function and its potential implications in the optimization of vascular grafts. β’ Keywords: DNMT1, cPLA2, Geometric constraint, Mitochondrial DNA methylation, Smooth muscle contractility β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration, mtDNA;mt-genetics
Organism: Human
Tissue;cell: Other cell lines
Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2022-09