PMID- 31062928 OWN - NLM STAT- MEDLINE DCOM- 20200619 LR - 20200619 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 13 IP - 8 DP - 2019 Aug TI - The cytoptrotection of small intestinal submucosa-derived gel in HL-1 cells during hypoxia/reoxygenation-induced injury. PG - 1346-1361 LID - 10.1002/term.2878 [doi] AB - Small intestinal submucosa (SIS)-derived gel injected into infarcted myocardium has been shown to promote repair and regeneration after myocardial infarction (MI); however, the specific impact of SIS gel on cardiomyocytes remained unknown. The aim of this study was to characterise SIS gel function in hypoxia-reoxygenation (H/R)-induced cardiomyocyte damage and its potential mechanism. HL-1 cardiomyocytes seeded on SIS matrix-coated plates, SIS gel, and uncoated plates were subjected to H/R, cell viability, apoptosis, expression of caspase-3, Bcl-2, and Bax were investigated. SIS gel and SIS matrix as coating substrates markedly improved cell viability, preventing cell apoptosis compared with uncoated plates, with SIS gel yielding the best cytoprotective effects. SIS gel down-regulated expression of pro-inflammatory cytokines (TNF-alpha, CCL2, and IL-6) by inhibiting the JNK-mitogen-activated protein kinase (MAPK)/NF-kappaB pathways. Furthermore, SIS gel protected cardiomyocytes from apoptosis by activating protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK) pathways, and markedly up-regulated antiapoptotic Bcl-2 expression but inhibited that of proapoptotic Bax and c-caspase 3. Together, these findings show that SIS gel could decrease H/R-induced cell apoptosis through a mechanism potentially related to its ability to regulate expression of inflammatory cytokines and antiapoptosis signalling pathways to prevent cell apoptosis. Our findings thereby shed light on the mechanism related to SIS gel therapeutic efficacy for MI. CI - (c) 2019 John Wiley & Sons, Ltd. FAU - Wang, Su-Ya AU - Wang SY AUID- ORCID: 0000-0002-2825-9212 AD - Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Sang, Jiang-Wei AU - Sang JW AD - Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Ding, Wei AU - Ding W AD - Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Qin, Ting-Wu AU - Qin TW AD - Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Bai, Lin AU - Bai L AD - Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Zhang, Jie AU - Zhang J AD - Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China. FAU - Luo, Jing-Cong AU - Luo JC AUID- ORCID: 0000-0003-3251-4105 AD - Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. LA - eng GR - 2012JY0082/National Basic Research Program of Sichuan Province/International GR - 2013SZ0088/National Basic Research Program of Sichuan Province/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190718 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Gels) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cell Hypoxia/drug effects MH - Cell Line MH - Cell Survival/drug effects MH - *Cytoprotection/drug effects MH - Gels/*pharmacology MH - Inflammation/pathology MH - Intestinal Mucosa/*chemistry MH - Intestine, Small/*chemistry MH - Mice MH - Oxygen OTO - NOTNLM OT - SIS gel OT - apoptosis OT - cardiomyocyte OT - cytoprotection OT - hypoxia/reoxygenation injury OT - inflammation EDAT- 2019/05/08 06:00 MHDA- 2020/06/20 06:00 CRDT- 2019/05/08 06:00 PHST- 2018/07/04 00:00 [received] PHST- 2019/03/25 00:00 [revised] PHST- 2019/04/29 00:00 [accepted] PHST- 2019/05/08 06:00 [pubmed] PHST- 2020/06/20 06:00 [medline] PHST- 2019/05/08 06:00 [entrez] AID - 10.1002/term.2878 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2019 Aug;13(8):1346-1361. doi: 10.1002/term.2878. Epub 2019 Jul 18.