Abstract
Connexin 43 (Cx43) may be important in cell death and survival due to cell-to-cell communication-independent mechanisms. In our previous study, we found that small G protein signaling modulator 3 (SGSM3), a partner of Cx43, contributes to myocardial infarction (MI) in rat hearts. Based on these previous results, we hypothesized that SGSM3 could also play a role in bone marrow-derived rat mesenchymal stem cells (MSCs), which differentiate into cardiomyocytes and/or cells with comparable phenotypes under low oxygen conditions. Cx43 and Cx43-related factor expression profiles were compared between normoxic and hypoxic conditions according to exposure time, and Sgsm3 gene knockdown (KD) using siRNA transfection was performed to validate the interaction between SGSM3 and Cx43 and to determine the roles of SGSM3 in rat MSCs. We identified that SGSM3 interacts with Cx43 in MSCs under different oxygen conditions and that Sgsm3 knockdown inhibits apoptosis and cardiomyocyte differentiation under hypoxic stress. SGSM3/Sgsm3 probably has an effect on MSC survival and thus therapeutic potential in diseased hearts, but SGSM3 may worsen the development of MSC-based therapeutic approaches in regenerative medicine. This study was performed to help us better understand the mechanisms involved in the therapeutic efficacy of MSCs, as well as provide data that could be used pharmacologically.
Highlights
Mesenchymal stem cells (MSCs) can isolated various sources including bone marrow, trabecular and cortical bone, adipose tissue, skeletal muscle, peripheral blood, umbilical cord blood, and dental pulp and differentiate into multi-lineage according to sources such as osteoblast, chondrocytes, adipocytes, cardiomyocytes, tenocytes, muscle cells, fibroblast, and neuron [1,2,3,4,5]
Small G protein signaling modulator 3 (SGSM3), a Connexin 43 (Cx43)-interacting protein, was confirmed in rat hearts [29]. We carried out these three analyses in rat MSCs as preliminary experiments and showed that there was an interaction between Cx43 and SGSM3 in MSCs
Cx43 and Cx43-related factor expression profiles in MSCs were first compared between normoxic and hypoxic conditions according to exposure times
Summary
Mesenchymal stem cells (MSCs) can isolated various sources including bone marrow, trabecular and cortical bone, adipose tissue, skeletal muscle, peripheral blood, umbilical cord blood, and dental pulp and differentiate into multi-lineage according to sources such as osteoblast, chondrocytes, adipocytes, cardiomyocytes, tenocytes, muscle cells, fibroblast, and neuron [1,2,3,4,5]. There has been tremendous focus on attempts to repair cardiac tissue. Small G protein signaling modulator 3 (SGSM3) knockdown attenuates apoptosis and cardiogenic differentiation and Engineering Foundation grants funded by the Korean government (MEST) (NRF2015M3A9E6029519) to KCH
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