PMID- 37123908 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230502 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 4 DP - 2023 Apr TI - FIR-preconditioning promotes Akt-mTOR-exosome manufacture in cooperation with MITF to boost resilience of rat bone marrow-derived stem cells. PG - e15003 LID - 10.1016/j.heliyon.2023.e15003 [doi] LID - e15003 AB - A previous study from our laboratory observed the protective effects of far-infrared irradiation (FIR) on bone marrow-derived stem cells (BMSCs) against oxidative stress. However, it remains unknown precisely how FIR influences BMSC survival. We identify an unexpected route among the expression of MITF, BCL2, mTOR, and exosome in FIR-preconditioned BMSCs. MITF siRNA demonstrated that loss of MITF expression not only inhibited cell proliferation but also reduced the FIR-mediated expression of mTOR, BCL2, and exosome. mTOR signaling pathways have been implicated in cell growth, proliferation, and survival. We also found that rapamycin, a potent and selective inhibitor of mTOR, when combined with MITF siRNA, repressed FIR-mediated CD63 and BCL2 expression. In addition, FIR-preconditioned BMSCs demonstrated more tolerance in multiple stressful environments than untreated BMSCs. The elevated exosomes in conditioned medium derived from FIR-preconditioned BMSCs also repaired H9c2 cells that sustained cellular damage after subjected to an array of environmental stress conditions. Taken together, these results reveal a possible mechanism about how FIR-preconditioned BMSCs and its conditioned media could contribute to cellular resilience during environmental changes via MITF-Akt-mTOR associated with exosome manufacture. FIR preconditioning could thus complement and improve therapeutic applications of BMSCs on outcomes of various disorders. CI - (c) 2023 Tech Unversity of Korea. FAU - Jeong, Yun-Mi AU - Jeong YM AD - Department of Mechanical Engineering, Tech University of Korea, 237 Sangidaehak Street, Si-heung City, Republic of Korea. FAU - Kim, Weon AU - Kim W AD - Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea. LA - eng PT - Journal Article DEP - 20230407 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10130773 OTO - NOTNLM OT - Akt/mTOR/exosome manufacture OT - Bone marrow-derived mesenchymal/stromal cells OT - Cellular resilience OT - Far-infrared irradiation OT - MITF COIS- All authors declare no competing interest. EDAT- 2023/05/01 06:42 MHDA- 2023/05/01 06:43 PMCR- 2023/04/07 CRDT- 2023/05/01 03:35 PHST- 2022/06/30 00:00 [received] PHST- 2023/03/21 00:00 [revised] PHST- 2023/03/23 00:00 [accepted] PHST- 2023/05/01 06:43 [medline] PHST- 2023/05/01 06:42 [pubmed] PHST- 2023/05/01 03:35 [entrez] PHST- 2023/04/07 00:00 [pmc-release] AID - S2405-8440(23)02210-7 [pii] AID - e15003 [pii] AID - 10.1016/j.heliyon.2023.e15003 [doi] PST - epublish SO - Heliyon. 2023 Apr 7;9(4):e15003. doi: 10.1016/j.heliyon.2023.e15003. eCollection 2023 Apr.