PMID- 37919806 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231105 IS - 1749-8546 (Print) IS - 1749-8546 (Electronic) IS - 1749-8546 (Linking) VI - 18 IP - 1 DP - 2023 Nov 2 TI - Xinyang tablet ameliorates sepsis-induced myocardial dysfunction by regulating Beclin-1 to mediate macrophage autophagy and M2 polarization through LncSICRNT1 targeting E3 ubiquitin ligase TRAF6. PG - 143 LID - 10.1186/s13020-023-00832-7 [doi] LID - 143 AB - OBJECTIVE: Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). METHODS: A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. RESULTS: Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. CONCLUSION: The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement. CI - (c) 2023. The Author(s). FAU - Luo, Yuanyuan AU - Luo Y AD - Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Li, Yuanmei AU - Li Y AD - Department of Rehabilitation Medicine, Nanfang Hospital of Southern Medical University, Guangzhou, China. FAU - He, Liwei AU - He L AD - Department of Cardiology, Nanfang Hospital of Southern Medical University, Guangzhou, China. FAU - Tu, Haitao AU - Tu H AD - Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Lin, Xinfeng AU - Lin X AD - Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhao, Fengli AU - Zhao F AD - Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Huang, Yusheng AU - Huang Y AD - Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Wen, Minyong AU - Wen M AD - Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Wang, Lingjun AU - Wang L AD - Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yang, Zhongqi AU - Yang Z AD - President's Office, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. ZhongqiY0122@163.com. LA - eng GR - 82104764/Mechanism of invigorating Qi, warming Yang, and activating blood circulation in the treatment of sepsis-induced myocardial dysfunction by regulating macrophage polarization through LncSICRNT1-mediated Beclin-1 ubiquitination/ PT - Journal Article DEP - 20231102 PL - England TA - Chin Med JT - Chinese medicine JID - 101265109 PMC - PMC10621131 OTO - NOTNLM OT - Beclin-1 OT - LncSICRNT1 OT - M1/M2 polarization OT - Macrophages OT - Sepsis-induced myocardial dysfunction OT - TRAF6 OT - Ubiquitination OT - Xinyang tablet COIS- The authors have no relevant financial or non-financial interests to disclose. EDAT- 2023/11/03 06:44 MHDA- 2023/11/03 06:45 PMCR- 2023/11/02 CRDT- 2023/11/03 00:57 PHST- 2023/03/20 00:00 [received] PHST- 2023/09/05 00:00 [accepted] PHST- 2023/11/03 06:45 [medline] PHST- 2023/11/03 06:44 [pubmed] PHST- 2023/11/03 00:57 [entrez] PHST- 2023/11/02 00:00 [pmc-release] AID - 10.1186/s13020-023-00832-7 [pii] AID - 832 [pii] AID - 10.1186/s13020-023-00832-7 [doi] PST - epublish SO - Chin Med. 2023 Nov 2;18(1):143. doi: 10.1186/s13020-023-00832-7.