Open AccessChitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis
Author(s) -
Norihisa Nishimura,
Davide De Battista,
David R. McGivern,
Ronald E. Engle,
Ashley Tice,
Rafaelle Fares-Gusmao,
Juraj Kabát,
Anna Pomerenke,
Hanh Nguyen,
Shinya Sato,
Kevin W. Bock,
Ian N. Moore,
David E. Kleiner,
Fausto Zamboni,
Harvey J. Alter,
Sugantha Govindarajan,
Patrizia Farci
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019633118
Subject(s) - cirrhosis , hepatic stellate cell , biology , fibrosis , hepatitis c virus , in situ hybridization , hepatic fibrosis , hepatitis c , gene expression , cancer research , pathology , virus , medicine , immunology , endocrinology , gene , biochemistry
Significance Older age at the time of hepatitis virus infection and age of liver donors are major determinants of liver fibrosis progression and disease severity. Our study demonstrates that aging is accompanied by significant changes in gene expression and identifies a gene,chitinase 3-like 1 (CHI3L1 ), as having the greatest age-dependent increase in expression and as being overexpressed in cirrhotic livers. Our in vivo and in vitro results provide evidence that CHI3L1 plays a central role in liver fibrogenesis and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression. This study may open avenues for specific antifibrotic or microRNA therapy to reduce or prevent hepatic fibrosis and its ominous complications.