Telomerase and Myocardin-A synergistically regulates expression of promyogenic transcription factors in mesenchymal stem cells of adult adipose tissue 

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	Presenter
	Presenter
Geng, Yong-Jian (United States of America)

List of Authors:

Rosalinda Madonna, Raffaele De Caterina, James T Willerson, Yong-Jian Geng

Abstract:

Background and Objective: Myocardin A (Myoc-A) and telomerase are two nuclear proteins coexpressed in cardiovascular myogenic stem cells. Myoc-A acts as a nuclear transcription cofactor for myogenic gene transcription while telomerase maintains the telomere length and prevents cellular senescence. An interaction or synergy between Myoc-A and the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT) may occur during the development of myogenic stem cells. The current study was designed to test expression of myogenic factors in mesenchymal stem cells (MSCs) with overexpression and interruption of Myoc-A and/or TERT functions.

Methods and Results: TERT and Myoc-A were transduced with cDNA constructs from coding sequences, and co-immunoprecipitated in murine MSCs isolated from adult adipose tissue. MSCs with expressed TERT and Myoc-A exhibited increased proliferation and differentiation, while retaining high levels of myogenic markers in the nuclei. In contrast, treatment with siRNA for TERT or Myoc-A inhibited the cell proliferation and differentiation. siRNA for TERT or Myoc-A reduced also expression of the promyogenic transcription factors Oct-4, Nkx2.5 and MLC2v as determined by qRT-PCR. The siRNA treatment decreased MEF2 expression in the nuclei as demonstrated by immunoblotting but the total cellular MEF2 protein contents remained unchanged.

Furthermore, MSCs with co-expression of TERT and Myoc-A showed activation of myogenic program as strong shift signals were detected in the nuclear proteins mixed with radioactive oligonucleotide probes produced from the consensus sequence for the serum response element (SRE), key for expression of many myogenic genes.

Conclusions: Co-expression of TERT and Myoc-A promotes myogenic development of MSCs from adult adipose tissue by promoting expression of promyogenic nuclear factors and by activating the SRE-containing promoters. These activities can be inhibited by TERT or Myoc-A siRNA treatment. Our data suggest that TERT and Myoc-A may have a synergy in regulation of cardiovascular myogenic development, potentially important for cardiac regenerative medicine.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.