PMID- 32271805 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20231113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 4 DP - 2020 TI - Small G protein signaling modulator 3 (SGSM3) knockdown attenuates apoptosis and cardiogenic differentiation in rat mesenchymal stem cells exposed to hypoxia. PG - e0231272 LID - 10.1371/journal.pone.0231272 [doi] LID - e0231272 AB - 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. FAU - Jung, Seung Eun AU - Jung SE AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. FAU - Choi, Jung-Won AU - Choi JW AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. FAU - Moon, Hanbyeol AU - Moon H AD - Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul, Republic of Korea. FAU - Oh, Sena AU - Oh S AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. FAU - Lim, Soyeon AU - Lim S AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. AD - International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea. FAU - Lee, Seahyoung AU - Lee S AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. AD - International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea. FAU - Kim, Sang Woo AU - Kim SW AUID- ORCID: 0000-0002-3144-4822 AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. AD - International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea. FAU - Hwang, Ki-Chul AU - Hwang KC AD - Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea. AD - International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200409 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Biomarkers) RN - 0 (Connexin 43) RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) RN - EC 3.6.5.2 (Sgsm3 protein, rat) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Biomarkers/metabolism MH - Cell Differentiation/*drug effects MH - Cell Hypoxia/drug effects MH - Connexin 43/metabolism MH - Gap Junctions/drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - *Gene Knockdown Techniques MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Mesenchymal Stem Cells/*cytology/drug effects/*metabolism MH - Monomeric GTP-Binding Proteins/*metabolism MH - Myocytes, Cardiac/drug effects/*metabolism MH - Oxygen/pharmacology MH - Rats, Sprague-Dawley MH - Stress, Physiological/drug effects MH - Time Factors MH - Wnt Signaling Pathway/drug effects PMC - PMC7145021 COIS- The authors have declared that no competing interests exist. EDAT- 2020/04/10 06:00 MHDA- 2020/07/14 06:00 PMCR- 2020/04/09 CRDT- 2020/04/10 06:00 PHST- 2020/02/04 00:00 [received] PHST- 2020/03/19 00:00 [accepted] PHST- 2020/04/10 06:00 [entrez] PHST- 2020/04/10 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2020/04/09 00:00 [pmc-release] AID - PONE-D-20-02560 [pii] AID - 10.1371/journal.pone.0231272 [doi] PST - epublish SO - PLoS One. 2020 Apr 9;15(4):e0231272. doi: 10.1371/journal.pone.0231272. eCollection 2020.