4.6 Article

Mitochondrial gene COX2 methylation and downregulation is a biomarker of aging in heart mesenchymal stem cells

Journal

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 47, Issue 1, Pages 161-170

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2020.4799

Keywords

mitochondria; cytochrome c oxidase subunit II; methylation; senescence; mesenchymal stem cell

Funding

  1. Jilin International Collaboration Grant [20180414065GH, 20190701040GH]
  2. Subject Arrangement Program from Science and Technology Department of Jilin Province [20200201123JC]
  3. Youth Development Programme of Health Commission of Jilin Province [2019Q007]
  4. Health Special Fund from Jilin Province Department of Finance [2018SCZWSZX-048]
  5. National Natural Science Foundation of China [81701270]
  6. Transformation Fund of the First Hospital of Jilin University [JDYYZH-1902033]
  7. China Postdoctoral Science Foundation [171251]
  8. Science-technology Foundation of the Jilin Provincial Education Department [JJKH20170823KJ]
  9. Norman Bethune Program of Jilin University [2015326]

Ask authors/readers for more resources

The study utilized human heart mesenchymal stem cells to construct two aging models and found that COX2 methylation and downregulation are biomarkers of HMSC senescence. Further investigation is needed to determine if COX2 has potential as a therapeutic target for cardiovascular diseases.
The mitochondria have been proven to be involved in processes of aging; however, the mechansims through which mitoepigenetics affect the cytological behaviors of cardiomyocytes during the aging process are not yet fully understood. In the present study, two senescence models were constructed, replicative senescence (RS) and stress-induced premature senescence (SIPS), using human heart mesenchymal stem cells (HMSCs). First, the differences in age-related gene expression levels and telomere length were compared between the HMSCs in the RS and SIPS models by PCR. Subsequently, protein expression and the mitochondrial DNA (mtDNA) methylation status of cytochrome c oxidase subunit II (COX2) was measured by western blot analysis and bisulfite genomic sequencing (BSP). Finally, the value of the DNA methyltransferase (Dnmt) inhibitor, 5-aza-2 '-deoxycytidine (AdC), in delaying the senescence of HMSCs was evaluated. It was found that the p16, p27 and p53 mRNA expression levels increased in the senescent cells, whereas p21 mRNA expression did not. It was also found that telomere shortening only occurred in the RS model, but not in the SIPS model. Along with the senescence of HMSCs, COX2 gene methylation increased and its protein expression level significantly decreased. It was demonstrated that AdC inhibited COX2 methylation and downregulated COX2 expression. The addition of exogenous COX2 or the administration of AdC promoted cell proliferation and delayed cell aging. On the whole, the present study demonstrates that COX2 methylation and downregulation are biomarkers of HMSC senescence. Thus, COX2 may have potential for use as a therapeutic target of cardiovascular diseases and this warrants further investigation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available