PMID- 38105228 OWN - NLM STAT- MEDLINE DCOM- 20240131 LR - 20240402 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 21 IP - 1 DP - 2023 Dec 17 TI - Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries. PG - 916 LID - 10.1186/s12967-023-04796-y [doi] LID - 916 AB - Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway. CI - (c) 2023. The Author(s). FAU - Fang, Qing AU - Fang Q AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Jing, Guoqing AU - Jing G AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Zhang, Ying AU - Zhang Y AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Wang, Hongyu AU - Wang H AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Luo, Huan AU - Luo H AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Xia, Yun AU - Xia Y AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Jin, Qiyan AU - Jin Q AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Liu, Yuping AU - Liu Y AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Zuo, Jing AU - Zuo J AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Yang, Cheng AU - Yang C AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. FAU - Zhang, Xiaodong AU - Zhang X AD - College of Life Sciences at, Wuhan University, Wuchang, 299 Bayi Road, Wuhan, 430072, Hubei Province, China. FAU - Liu, Shi AU - Liu S AD - College of Life Sciences at, Wuhan University, Wuchang, 299 Bayi Road, Wuhan, 430072, Hubei Province, China. FAU - Wu, Xiaojing AU - Wu X AD - Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuchang, 238 Liberation Road, Wuhan, 430060, Hubei Province, China. wxj164@163.com. FAU - Song, Xuemin AU - Song X AD - The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuchang, 169 Donghu Road, Wuhan, 430071, Hubei Province, China. xueminsong@whu.edu.cn. LA - eng GR - 81571941/National Natural Science Foundation of China/ GR - 82172144/National Natural Science Foundation of China/ GR - 81901952/National Natural Science Foundation of China/ GR - 82372156/National Natural Science Foundation of China/ PT - Journal Article DEP - 20231217 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Erbb2ip protein, mouse) RN - 0 (Tcfeb protein, mouse) RN - 0 (Intracellular Signaling Peptides and Proteins) SB - IM MH - Animals MH - Mice MH - Autophagosomes/metabolism MH - Autophagy/genetics MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism MH - *Cell Nucleus/metabolism MH - Inflammation/etiology/genetics/metabolism MH - Lysosomes/genetics/metabolism MH - *Sepsis/complications MH - *Intracellular Signaling Peptides and Proteins/metabolism PMC - PMC10725606 OTO - NOTNLM OT - Autophagy OT - Erbin OT - Lysosome OT - Sepsis OT - TFEB COIS- The authors have no relevant financial or non-financial interests to disclose. EDAT- 2023/12/18 00:42 MHDA- 2023/12/19 06:42 PMCR- 2023/12/17 CRDT- 2023/12/17 23:33 PHST- 2023/10/21 00:00 [received] PHST- 2023/12/09 00:00 [accepted] PHST- 2023/12/19 06:42 [medline] PHST- 2023/12/18 00:42 [pubmed] PHST- 2023/12/17 23:33 [entrez] PHST- 2023/12/17 00:00 [pmc-release] AID - 10.1186/s12967-023-04796-y [pii] AID - 4796 [pii] AID - 10.1186/s12967-023-04796-y [doi] PST - epublish SO - J Transl Med. 2023 Dec 17;21(1):916. doi: 10.1186/s12967-023-04796-y.