Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1

Xie, Si An; Zhang, Tao; Wang, Jin; Zhang, Feng; Zhang, Yun Peng; Yao, Wei; Hur, Sung Sik; Yeh, Yi Ting; Pang, Wei; Li, Zheng; Fan, Yi; Kong, Wei; Wang, Xian; Chiu, Jeng Jiann; Zhou, Jing

doi:10.1016/j.biomaterials.2017.11.033

Cited by 106 publications

(93 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, DNA methylation modulates the expression of SMC phenotypic markers, such as SM22α and alkaline phosphatase 41,42 . Our previous study also showed that in vascular SMCs, DNMT1 is important for the matrix stiffness-induced phenotypic switch and its deficiency causes arterial stiffening, likely attributable to nuclear DNMT1 43 . In the current study, we revealed a different role of mitochondrial DNMT1 in regulating the contractile phenotype of vascular SMC, extending our understanding of the role of DNA methylation in directing SMC phenotype through regulating mitochondrial bioenergetics-related mtDNAencoded gene transcription (Figs.…”

Section: Discussionmentioning

confidence: 65%

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

et al. 2020

Self Cite

View full text Add to dashboard Cite

Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease.

show abstract

Section: Discussionmentioning

confidence: 65%

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The upstream genes of this pathway are involved in the synthesis of collagen. Collagen is an important component of the ECM [10] , and plays an important role in the occurrence and development of tumors [11,12] . It has also be shown that collagen acts as a barrier against the invasion and metastasis of tumor cells [13] .…”

Section: Discussionmentioning

confidence: 99%

Analysis of Proteomic Differences between Eutopic Endometrium and Ectopic Endometrium in Patients with Endometriosis

Chen¹,

Zhao²,

An³

et al. 2020

Preprint

View full text Add to dashboard Cite

Objective To analyze the difference in protein expression between eutopic endometrium and ectopic endometrium from a proteomic aspect, to investigate a preclinical research basis in the occurrence and development of endometriosis (EMT), and provide a theoretical basis for new diagnosis and treatment of EMT. Methods Eutopic and ectopic endometrium tissue were collected from 8 patients with an ovarian endometriotic cyst. The protein was extracted for the screening of differential proteins, database retrieval and bioinformatics. Functional classification of differential proteins was performed by gene ontology (GO), secondary annotation, and subcellular structure positioning. The functions of the proteins were analyzed by GO, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein domain enrichments. Results were further validated by clustering analysis. Results Among a total of 6,233 identified proteins, 5,395 proteins had quantitative information, including 190 up-regulated proteins and 153 down-regulated proteins. Bioinformatics of differential proteins showed that the up-regulated proteins were primarily distributed in the nuclei and closely associated with conformation change of DNA and ribosome duplication, while the down-regulated proteins were predominantly distributed in the extracellular, cytoplasmic membrane and other positions and were related to the migration of endometrial tissues. Conclusion The differential expression of proteins in eutopic endometrium and ectopic endometrium plays an important role in the occurrence and development of EMT and its resultant infertility. The proteomic analysis provides a new basis for future research investigating the pathogenesis of EMT.

show abstract

“…After screening through 224 articles, we identified 66 original reports examining epigenetic processes in VC ( Figure 1). Interestingly, most reports (n = 40; 60.6%) looked into the pathogenic role of non-coding RNA in VC, while histone modification (n = 6; 9.1%) [53][54][55][56][57][58], DNA methylation (n = 8; 12.1%) [5,[59][60][61][62][63][64][65], and chromatin changes (n = 3; 4.5%) [66][67][68] accounted for one-fourth only. Nine (13.6%) [69][70][71][72][73][74][75][76][77] examined the discrepancy of epigenetic signatures between subjects or animals with and without VC but not their pathogenic influences.…”

Section: Strategy Of Literature Review and Findingsmentioning

confidence: 99%

“…A total of eight articles evaluate the influence of DNA methylation in the process of VC, ranging from in vitro to in vivo settings [5,[59][60][61][62][63][64][65]. Common precipitators of VC, including HP environment, uremic toxin (indoxyl sulfate (IS)), and extracellular matrix constituents, have all been found to intensify the severity of VC through changes in methylation status of specific genes involved in osteoblastic differentiation.…”

Section: Dna Methylation In Vcmentioning

confidence: 99%

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

Hou

Yuan

et al. 2020

IJMS

View full text Add to dashboard Cite

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

show abstract

Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1

Cited by 106 publications

References 42 publications

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

Analysis of Proteomic Differences between Eutopic Endometrium and Ectopic Endometrium in Patients with Endometriosis

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

Contact Info

Product

Resources

About