PMID- 36242919 OWN - NLM STAT- MEDLINE DCOM- 20221108 LR - 20221206 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 634 DP - 2022 Dec 17 TI - YAP affects the efficacy of liver progenitor cells transplantation in CCl(4)-induced acute liver injury. PG - 129-137 LID - S0006-291X(22)01390-0 [pii] LID - 10.1016/j.bbrc.2022.10.005 [doi] AB - The liver is a highly regenerative organ. During acute liver injury, the remaining hepatocytes rapidly proliferate to restore liver parenchyma and liver function. However, hepatocytes-driven regeneration is compromised in severe liver injury; instead, liver progenitor cells (LPCs) proliferate and differentiate into hepatocytes or cholangiocytes to restore mass and function of liver. The Hippo signaling pathway is of vital importance in liver regeneration, and Yes-associated protein (YAP) is the key component of the Hippo pathway. The therapeutic role of YAP has been well studied in hepatocytes-driven liver regeneration. However, the role of LPCs transplantation in acute liver injury has not been defined. Here, we investigated the therapeutic effect of splenic-transplantation of LPCs in CCl(4)-induced acute liver injury and explored the role of YAP during the procedure. LPCs isolated from choline-deficient, ethionine-supplemented diet (CDE) model were infected with GFP-YAP cDNA lentiviral vector, GFP-YAP shRNA lentiviral vector, and GFP lentiviral vector as control, respectively. At 48 h after CCl(4) injection, PBS (control group), GFP lentiviral vector-infected LPCs (GFP-LPC group), GFP-YAP cDNA lentiviral vector-infected LPCs (YAP-LPC group) and GFP-YAP shRNA lentiviral vector-infected LPCs (sh-YAP-LPC group) were injected into spleens in CCl(4)-treated mice. Histological and serological analyses were performed to evaluate pathology and liver function. The effect of LPCs on the proliferation of hepatocytes and inflammation was investigated. We demonstrated that intra-splenic transplantation of LPCs alleviates CCl(4)-induced acute liver injury and YAP signaling acts a key role during the procedure. Further studies suggested that LPCs alleviate acute liver injury by promoting pre-existing hepatocytes proliferation rather than differentiating into hepatocytes. Furthermore, intra-splenic transplantation of LPCs attenuates inflammation, which facilitates tissue repair in acute liver injury. In conclusion, LPCs transplantation is a potential treatment for acute liver injury and YAP is a prospective therapeutic target in acute liver injury. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Dai, Weiming AU - Dai W AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Shen, Zhenyang AU - Shen Z AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Guo, Yuecheng AU - Guo Y AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Wang, Junjun AU - Wang J AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Li, Xiaoman AU - Li X AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Wang, Jianxiang AU - Wang J AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Lu, Lungen AU - Lu L AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. FAU - Cai, Xiaobo AU - Cai X AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. Electronic address: caixiaobo1979@hotmail.com. FAU - Li, Yan AU - Li Y AD - Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200000, China. Electronic address: liyan19841231@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221005 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (RNA, Small Interfering) RN - 0 (DNA, Complementary) SB - IM MH - Mice MH - Animals MH - RNA, Small Interfering/metabolism MH - DNA, Complementary/metabolism MH - *Liver/metabolism MH - *Liver Regeneration MH - Stem Cells MH - Hepatocytes MH - Cell Proliferation MH - Inflammation/pathology OTO - NOTNLM OT - Acute liver injury OT - Inflammation OT - Liver progenitor cells OT - Liver regeneration OT - Yes-associated protein COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lungen Lu reports financial support was provided by the National Natural Science Foundation of China. Lungen Lu reports a relationship with the National Natural Science Foundation of China that includes: funding grants.. EDAT- 2022/10/16 06:00 MHDA- 2022/11/09 06:00 CRDT- 2022/10/15 18:26 PHST- 2022/09/25 00:00 [received] PHST- 2022/09/27 00:00 [revised] PHST- 2022/10/01 00:00 [accepted] PHST- 2022/10/16 06:00 [pubmed] PHST- 2022/11/09 06:00 [medline] PHST- 2022/10/15 18:26 [entrez] AID - S0006-291X(22)01390-0 [pii] AID - 10.1016/j.bbrc.2022.10.005 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2022 Dec 17;634:129-137. doi: 10.1016/j.bbrc.2022.10.005. Epub 2022 Oct 5.