Research Paper Volume 13, Issue 1 pp 957—972
Bnip3 interacts with vimentin, an intermediate filament protein, and regulates autophagy of hepatic stellate cells
- 1 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- 2 Department of Surgery, Wuhan Third Hospital, Wuhan, PR China
- 3 Department of Hospital Infection Management, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- 4 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- 5 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- 6 Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
Received: April 19, 2020 Accepted: September 9, 2020 Published: December 3, 2020https://doi.org/10.18632/aging.202211
How to Cite
Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Bnip3, which is regulated by Hif-1 in cells under oxygen deprivation, is a death related protein associated with autophagy and apoptosis. Hif-1 was reported to regulate autophagy to activate hepatic stellate cells (HSCs), while the specific molecular mechanism is vague. The possible mechanism of Hif-1 regulating autophagy of HSCs via Bnip3 was explored in this study. Bnip3 was detected in fibrotic liver tissues from humans and mice. Hif-1 was inhibited by chemical inhibitor and Bnip3 was detected in activated HSCs. The co-localization of Bnip3 and LC3B was captured by confocal microscopy and autophagic flow was assessed in Bnip3 siRNA transfected cells. Bnip3 interacted proteins were screened with mass spectrometry. The interaction of Bnip3 and vimentin was detected with co-immunoprecipitation and confocal microscopy. The results showed that Bnip3 was increased in fibrotic liver tissues and activated HSCs. Hif-1 inhibition suppressed Bnip3 expression in activated HSCs. Bnip3 was partially co-localized with autophagosomes and Bnip3 inhibition suppessed autophagy in activated HSCs. Bnip3 interacted with vimentin and Bnip3 expression was inhibited as vimentin was inhibited in activated HSCs. Conclusively, this study indicated that Bnip3 promoted autophagy and activation of HSCs, via interacting with vimentin, an intermediate filament protein with highly abundant expression in HSCs.
ECM: extracellular matrix; HSC: hepatic stellate cell; α-SMA: α-smooth muscle actin; LC3: microtubule-associated proteins light chain 3 alpha; ATG: autophagy-related gene; Bnip3: Bcl-2/adenovirus E1B 19-kDa interacting protein; BH3: Bcl-2 homology domain 3; mTOR: mammalian rapamycin target protein; Hif-1: hypoxia inducible factor-1; LPS: lipopolysaccharide; IF: intermediate filament; TLR: Toll-like receptor; HRE: hypoxia responsive element; GFAP: glial fibrillary acidic protein; WFA: Withaferin A.