例如:"lncRNA", "apoptosis", "WRKY"

Fam20C-mediated phosphorylation of osteopontin is critical for its secretion but dispensable for its action as a cytokine in the activation of hepatic stellate cells in liver fibrogenesis.

FASEB J.2020 Jan;34(1):1122-1135. doi:10.1096/fj.201900880R. Epub 2019 Nov 29
Elena Tibaldi 1 , Alessandra Brocca 2 , Antonietta Sticca 2 , Elisabetta Gola 2 , Marco Pizzi 3 , Luciana Bordin 1 , Mario Angelo Pagano 1 , Marco Mazzorana 4 , Gabriella Donà 1 , Paola Violi 5 , Oriano Marin 6 , Antonella Romano 2 , Paolo Angeli 2 , Amedeo Carraro 5 , Anna Maria Brunati 1
Elena Tibaldi 1 , Alessandra Brocca 2 , Antonietta Sticca 2 , Elisabetta Gola 2 , Marco Pizzi 3 , Luciana Bordin 1 , Mario Angelo Pagano 1 , Marco Mazzorana 4 , Gabriella Donà 1 , Paola Violi 5 , Oriano Marin 6 , Antonella Romano 2 , Paolo Angeli 2 , Amedeo Carraro 5 , Anna Maria Brunati 1
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular Medicine, University of Padova, Padova, Italy.
  • 2 Department of Medicine (DIMED), University of Padova, Padova, Italy.
  • 3 General Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy.
  • 4 Diamond Light Source, Ltd., Harwell Science and Innovation Campus, Didcot, UK.
  • 5 Department of General Surgery and Odontoiatrics, Liver Transplant Unit, University Hospital of Verona, Verona, Italy.
  • 6 Department of Biomedical Sciences, University of Padova, Padova, Italy.

摘要


Osteopontin (OPN) is a phosphoglycoprotein secreted into the extracellular matrix upon liver injury, acting as a cytokine stimulates the deposition of fibrillary collagen in liver fibrogenesis. In livers of mice subjected to bile duct ligation (BDL) and in cultured activated hepatic stellate cells (HSCs), we show that OPN, besides being overexpressed, is substantially phosphorylated by family with sequence similarity 20, member C (Fam20C), formerly known as Golgi casein kinase (G-CK), which is exclusively resident in the Golgi apparatus. In both experimental models, Fam20C becomes overactive when associated with a 500-kDa multiprotein complex, as compared with the negligible activity in livers of sham-operated rats and in quiescent HSCs. Fam20C knockdown not only confirmed the role of Fam20C itself in OPN phosphorylation, but also revealed that phosphorylation was essential for OPN secretion. However, OPN acts as a fibrogenic factor independently of its phosphorylation state, as demonstrated by the increased expression of Collagen-I by HSCs incubated with either a phosphorylated or nonphosphorylated form of recombinant OPN. Collectively, our results confirm that OPN promotes liver fibrosis and highlight Fam20C as a novel factor driving this process by favoring OPN secretion from HSCs, opening new avenues for deciphering yet unidentified mechanisms underlying liver fibrogenesis.

KEYWORDS: Golgi apparatus, bile duct ligation, hepatic stellate cells, osteopontin, phosphorylation