Imperial College London
Alternate

Dr Salvatore Papa

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 3313 8282s.papa

 
 
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Location

 

10N.13Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Arif:2021:10.1152/ajpgi.00105.2021,
author = {Arif, E and Wang, C and Swiderska-Syn, MK and Solanki, AK and Rahman, B and Manka, PP and Coombes, J and Canbay, A and Papa, S and Nihalani, D and Lipschutz, JH and Syn, W-K},
doi = {10.1152/ajpgi.00105.2021},
journal = {American Journal of Physiology: Gastrointestinal and Liver Physiology},
pages = {G1044--G105},
title = {Targeting myosin 1c inhibits murine hepatic fibrogenesis},
url = {http://dx.doi.org/10.1152/ajpgi.00105.2021},
volume = {320},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Myosin 1c (Myo1c) is an unconventional myosin that modulates signaling pathways involved in tissue injury and repair. In this study, we observed that Myo1c expression is significantly upregulated in human chronic liver disease such as nonalcoholic steatohepatitis (NASH) and in animal models of liver fibrosis. High throughput data from the GEO-database identified similar Myo1c upregulation in mice and human liver fibrosis. Notably, TGF-β stimulation to hepatic stellate cells (HSCs, the liver pericyte and key cell type responsible for the deposition of extracellular matrix upregulates Myo1c expression, while genetic depletion or pharmacological inhibition of Myo1c blunted TGF-β induced fibrogenic responses, resulting in repression of α-SMA and Col1α1 mRNA. Myo1c deletion also decreased fibrogenic processes such as cell proliferation, wound healing response and contractility when compared with vehicle treated HSCs. Importantly, phosphorylation of SMAD2 and SMAD3 were significantly blunted upon Myo1c inhibition in GRX cells as well as Myo1c-KO MEFs upon TGF-β stimulation. Using the genetic Myo1c knockout (Myo1c-KO) mice, we confirmed that Myo1c is critical for fibrogenesis as Myo1c-KO mice were resistant to CCl4 induced liver fibrosis. Histological and immunostaining analysis of liver sections showed that deposition of collagen fibers and α-SMA expression were significantly reduced in Myo1c-KO mice upon liver injury. Collectively, these results demonstrate that Myo1c-mediates hepatic fibrogenesis by modulating TGF-β signaling and suggest that inhibiting this process may have clinical application in treating liver fibrosis.
AU  - Arif,E
AU  - Wang,C
AU  - Swiderska-Syn,MK
AU  - Solanki,AK
AU  - Rahman,B
AU  - Manka,PP
AU  - Coombes,J
AU  - Canbay,A
AU  - Papa,S
AU  - Nihalani,D
AU  - Lipschutz,JH
AU  - Syn,W-K
DO  - 10.1152/ajpgi.00105.2021
EP  - 105
PY  - 2021///
SN  - 0193-1857
SP  - 1044
TI  - Targeting myosin 1c inhibits murine hepatic fibrogenesis
T2  - American Journal of Physiology: Gastrointestinal and Liver Physiology
UR  - http://dx.doi.org/10.1152/ajpgi.00105.2021
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33908271
UR  - http://hdl.handle.net/10044/1/89695
VL  - 320
ER  -
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