Insulin-Like Growth Factor Binding Protein-Related Protein 1 Activates Primary Hepatic Stellate Cells via Autophagy Regulated by the PI3K/Akt/mTOR Signaling Pathway
Authors: Yangyang Kong
Haiyan Zhang
Xiaohong Guo
Lixin Liu
Qianqian Zhang
Yuzheng Zhou
Huiqin Fan
Journal: Digestive Diseases and Sciences (2020)
Discipline: CLINICAL MEDICINE
Keywords: Autophagy; Hepatic stellate cells; IGFBPrP1; Liver fibrosis; PI3K/Akt/mTOR signaling pathway.
Affiliations: Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, China., Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China., Key Laboratory of Cell Physiology, Department of The Ministry of Education, Shanxi Medical University, 85 Jiefang South Road, Taiyuan, 030001, Shanxi Province, China., Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, China. ., Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China. ., Key Laboratory of Cell Physiology, Department of The Ministry of Education, Shanxi Medical University, 85 Jiefang South Road, Taiyuan, 030001, Shanxi Province, China. .

Abstract:  Background: Autophagy is a self-degrading process. Previously, we showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel transforming growth factor β1 (TGFβ1)-interacting factor in liver fibrosis; the role of TGFβ1-mediated autophagy in hepatic stellate cells (HSCs) activation has been investigated. However, whether autophagy is regulated by IGFBPrP1 remains unknown. Aims: We investigated the interactions among IGFBPrP1, autophagy, and activation of primary rat HSCs. Methods: Primary HSCs were separated from Sprague Dawley rats by two-step enzymatic digestion, and then, we overexpressed or inhibited IGFBPrP1 expression in HSCs under serum-starved condition. Autophagy inducer rapamycin or inhibitor 3-methyladenine (3MA) was used to assess the relationship between autophagy and HSCs activation. Results: We observed the expression of activation marker α-SMA and autophagy markers such as LC3B and Beclin1, which were significantly increased in HSCs treated with adenovirus vector harboring the IGFBPrP1 gene (AdIGFBPrP1) compared to cells cultured under serum-starved. In comparison, HSCs treated with shIGFBPrP1 showed opposite results. Furthermore, HSCs activation and autophagy increased when cells were treated with rapamycin, whereas opposite results were obtained when cells were treated with 3MA. AdIGFBPrP1 treatment downregulated the phosphorylation of Akt and mTOR. Conclusion: Autophagy was induced in IGFBPrP1-treated primary HSCs, and IGFBPrP1-induced autophagy promoted the activation of HSCs and extracellular matrix expression, the underlying mechanism of which may involve the phosphatidylinositide 3-kinase/Akt/mTOR signaling pathway. 

Retracted: No

PubPeer comments:
  The New India s Budget 2018e19 is projected as u2018budget for growth and prosperityu2019. Claimed to be the world s largest government funded health care program with ambitious initiatives such as Ayushman Bharat (AB) and National Health Protection Scheme (NHPS), the government is aiming to transform the public health care system.  The world morbidity statistics indicates urgent need for prevention and control of NCDs as the most important targets of UHC. Integrative interventions based on Ayurveda (diet and lifestyle modification) and Yoga (mind and body synergy) can play significant role in prevention of NCDs. NCDs = non-communicable diseases Could the authors kindly provide a comprehensive list of scientific studies that support the claim in the last sentence of the quote above? , 
  Integrative interventions based on Ayurveda (diet and lifestyle modification) and Yoga (mind and body synergy)... . The idea is very much in line with the themes of National Center for Complementary and Integrative Health, NIH. ,