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IGFBPrP1 accelerates autophagy and activation of hepatic stellate cells via mutual regulation between H19 and PI3K/AKT/mTOR pathway.
Biomed Pharmacother 2019; 116:109034BP

Abstract

BACKGROUND

Our previous study found that insulin-like growth factor binding protein-associated protein (IGFBPrP1) drives hepatic stellate cells (HSCs) activation, and IGFBPrP1 and transforming growth factor β1 (TGFβ1) likely interact with each other to promote HSCs activation. TGFβ1 reportedly promotes autophagy and contributes to HSCs activation; however, the mechanism between IGFBPrP1 and autophagy in liver fibrogenesis is yet unknown. Moreover, long noncoding RNA (lncRNA) H19 participates in autophagy regulation and plays a crucial function in liver fibrosis.

AIMS

To define the relationship between IGFBPrP1 and autophagy and the role of H19 in IGFBPrP1-induced hepatic fibrosis.

METHODS

IGFBPrP1 and autophagy were detected in bile duct ligation (BDL)-induced hepatic fibrosis. Adenovirus-mediated IGFBPrP1 was transfected into mouse liver and JS-1 cells with or without LY294002 or rapamycin to examine the effects of IGFBPrP1 on HSCs activation and autophagy as well as the PI3K/AKT/mTOR pathway. lncRNA H19 in liver fibrosis tissues and JS-1 cells induced by IGFBPrP1 were detected, then autophagy and HSCs activation level were detected in JS-1 cells by IGFBPrP1 with H19 overexpression or knowdown.

RESULTS

IGFBPrP1 expression and autophagy level were concomitantly increased in liver tissue with BDL-induced hepatic fibrosis. Furthermore, we found that IGFBPrP1 stimulated autophagy and HSCs activation in vivo and in vitro, and PI3K/AKT/mTOR signaling pathway was involved in the regulation of autophagy by IGFBPrP1. In addition, H19 promoted autophagy by interacting with the PI3K/AKT/mTOR pathway in IGFBPrP1-induced HSCs activation.

CONCLUSIONS

IGFBPrP1 promoted autophagy and contributed to HSCs activation via mutual regulation between H19 and the PI3K/AKT/mTOR pathway.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cell Physiology, Department of the Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: lixinliu6@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31152924

Citation

Huang, Ting-Juan, et al. "IGFBPrP1 Accelerates Autophagy and Activation of Hepatic Stellate Cells Via Mutual Regulation Between H19 and PI3K/AKT/mTOR Pathway." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 116, 2019, p. 109034.
Huang TJ, Ren JJ, Zhang QQ, et al. IGFBPrP1 accelerates autophagy and activation of hepatic stellate cells via mutual regulation between H19 and PI3K/AKT/mTOR pathway. Biomed Pharmacother. 2019;116:109034.
Huang, T. J., Ren, J. J., Zhang, Q. Q., Kong, Y. Y., Zhang, H. Y., Guo, X. H., ... Liu, L. X. (2019). IGFBPrP1 accelerates autophagy and activation of hepatic stellate cells via mutual regulation between H19 and PI3K/AKT/mTOR pathway. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 116, p. 109034. doi:10.1016/j.biopha.2019.109034.
Huang TJ, et al. IGFBPrP1 Accelerates Autophagy and Activation of Hepatic Stellate Cells Via Mutual Regulation Between H19 and PI3K/AKT/mTOR Pathway. Biomed Pharmacother. 2019;116:109034. PubMed PMID: 31152924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IGFBPrP1 accelerates autophagy and activation of hepatic stellate cells via mutual regulation between H19 and PI3K/AKT/mTOR pathway. AU - Huang,Ting-Juan, AU - Ren,Jun-Jie, AU - Zhang,Qian-Qian, AU - Kong,Yang-Yang, AU - Zhang,Hai-Yan, AU - Guo,Xiao-Hong, AU - Fan,Hui-Qin, AU - Liu,Li-Xin, Y1 - 2019/05/29/ PY - 2019/03/07/received PY - 2019/05/04/revised PY - 2019/05/22/accepted PY - 2019/6/4/pubmed PY - 2020/1/14/medline PY - 2019/6/2/entrez KW - Autophagy KW - Hepatic fibrosis KW - Hepatic stellate cells KW - Insulin-like growth factor binding protein-related protein 1 KW - LncRNA H19 KW - PI3K/AKT/mTOR SP - 109034 EP - 109034 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 116 N2 - BACKGROUND: Our previous study found that insulin-like growth factor binding protein-associated protein (IGFBPrP1) drives hepatic stellate cells (HSCs) activation, and IGFBPrP1 and transforming growth factor β1 (TGFβ1) likely interact with each other to promote HSCs activation. TGFβ1 reportedly promotes autophagy and contributes to HSCs activation; however, the mechanism between IGFBPrP1 and autophagy in liver fibrogenesis is yet unknown. Moreover, long noncoding RNA (lncRNA) H19 participates in autophagy regulation and plays a crucial function in liver fibrosis. AIMS: To define the relationship between IGFBPrP1 and autophagy and the role of H19 in IGFBPrP1-induced hepatic fibrosis. METHODS: IGFBPrP1 and autophagy were detected in bile duct ligation (BDL)-induced hepatic fibrosis. Adenovirus-mediated IGFBPrP1 was transfected into mouse liver and JS-1 cells with or without LY294002 or rapamycin to examine the effects of IGFBPrP1 on HSCs activation and autophagy as well as the PI3K/AKT/mTOR pathway. lncRNA H19 in liver fibrosis tissues and JS-1 cells induced by IGFBPrP1 were detected, then autophagy and HSCs activation level were detected in JS-1 cells by IGFBPrP1 with H19 overexpression or knowdown. RESULTS: IGFBPrP1 expression and autophagy level were concomitantly increased in liver tissue with BDL-induced hepatic fibrosis. Furthermore, we found that IGFBPrP1 stimulated autophagy and HSCs activation in vivo and in vitro, and PI3K/AKT/mTOR signaling pathway was involved in the regulation of autophagy by IGFBPrP1. In addition, H19 promoted autophagy by interacting with the PI3K/AKT/mTOR pathway in IGFBPrP1-induced HSCs activation. CONCLUSIONS: IGFBPrP1 promoted autophagy and contributed to HSCs activation via mutual regulation between H19 and the PI3K/AKT/mTOR pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/31152924/IGFBPrP1_accelerates_autophagy_and_activation_of_hepatic_stellate_cells_via_mutual_regulation_between_H19_and_PI3K/AKT/mTOR_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(19)30974-6 DB - PRIME DP - Unbound Medicine ER -