Hepatic stellate cells and hepatic stellate cell-derived extracellular matrix in acute liver injury.

• Applicant: Dr. Sonakshi Bhattacharjee, Ph.D.
• Subject Area: Gastroenterology ; Cell Biology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417747618

• Final Report Year: 2021

Final Report Abstract

In this project we investigated the myriad functions of hepatic stellate cells in the liver, focusing on acute liver injury and liver cancer. Overall, our studies show that HSC have context-specific functions and that they not only exert disease-promoting but also protective roles: Our findings establish protective functions of HSC in CCl4-, acetaminophen-driven acute liver injury and partial hepatectomy, mediated by the promotion of hepatocyte proliferation as well as the modulation of hepatocyte injury. On the other hand, HSC-derived cancer-associated fibroblasts have dual functions. HSC-CAF derived type 1 collagen restricts tumor growth while HSC-CAF derived hyaluronic acid (HA) and hepatocyte growth factor (HGF) promote tumor growth. Going forward the findings from this project may help to develop new therapeutic approaches to target the tumor promoting arm of CAF while leaving the liver protective/ tumor restrictive arm intact.

Publications

• Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell., 2021 Apr 29
  Affo S, Nair A, Brundu F, Ravichandra A, Bhattacharjee S, Matsuda M, Chin L, FilliolA,Wen W, Song X, Decker A, Worley J, Caviglia JM, Yu L, Yin D, Saito Y, Savage T,Wells R, Mack M, Zender L, Arpaia N, Remotti H E, Rabadan R, SimsP, Leblond AL, Weber A, Riener MO, Stockwell BR, Gaublomme J, Llovet JM., Michalopoulos GK, Seki E, Sia D, Chen X, Califano A, Schwabe RF
  (See online at https://doi.org/10.1177/1747493018778713)
• Tumor restriction by type I collagen opposes tumor-promoting effects of cancer- associated fibroblasts. J Clin Invest., 2021 Apr 27:146987
  Bhattacharjee S, Hamberger F, Ravichandra A, Miller M, Nair A, Affo S, FilliolA, Chin L,Savage TM,YinD,WirsikNM,Mehal A,Arpaia N,SekiE,Mack M,ZhuD,SimsPA, Stanger BZ, Olive KP, Schmidt T, Wells RG, Mederacke I, Schwabe RF
  (See online at https://doi.org/10.1172/jci146987)