Biochemical and Biophysical Research Communications
Expression and function of fibroblast growth factor (FGF) 9 in hepatic stellate cells and its role in toxic liver injury
Section snippets
Materials and methods
Preparation of cells and cell culture. Rat HSC were prepared from male Sprague–Dawley rats (about 500 g body weight) by the pronase/collagenase method as described before [6]. Hepatocytes were isolated following the collagenase method of Seglen as described [6]. Hepatocytes were seeded at a density of 5 × 104/cm2 on collagen coated dishes in Hepatozyme-SFM (Invitrogen, Heidelberg, Germany). Rat HSC, COS-1 cells, and the immortalized human hepatic stellate cell line LX-2 (a kind gift from Dr. S.L.
Expression of FGFR isoforms in HSC
Since FGF tyrosine kinase receptors bind FGFs with different binding affinities and alternative spliced variants exhibit unique FGF-binding specificity, we investigated the expression of the four FGF tyrosine kinase receptors in freshly isolated HSC and in HSC cultured for 3 days. To examine the expression of differentially spliced FGFR1, FGFR2, and FGFR3 isoforms by RT-PCR in detail, we first used oligonucleotide primers (set I depicted in Fig. 1A) that encompass the second half of Ig-like
Discussion
FGFs are thought to have a key role in tissue-repair processes and the involvement of HSC in liver regeneration and tissue repair is widely accepted. Here, we report for the first time that FGF9 is overexpressed in HSC during acute liver insult and we could show that FGF9 is highly mitogenic for primary hepatocytes suggesting that FGF9 secreted by HSC is acting in a paracrine mode on hepatocytes during liver repair. FGF9 is a secreted FGF and known to activate FGFR4, the main FGF receptor of
Acknowledgments
The authors are indebted to C. Kneip (Grünenthal GmbH, Aachen) and N. Sheron (University of Southampton) for their help and advice with the liver slice cultures. This work was supported by grants from the German Research Foundation to P.K. (KI 545/8-1) and C.H. (HE 2458/14-1).
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