c-Fos is necessary for HGF-mediated gene regulation and cell migration in Schwann cells

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.08.054· OSTI ID:23103611

Ko, Kyeong Ryang ^[1]; Lee, Junghun ^[2]; Nho, Boram; Kim, Sunyoung ^[1]

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1. School of Biological Sciences, Seoul National University, Seoul, 08826, South (Korea, Republic of)
2. ViroMed, Co., Ltd, Seoul, 08826, South (Korea, Republic of)

Highlights: • HGF up-regulates c-Fos expression in distal SCs in injured sciatic nerves. • HGF increase c-Fos expression in primary Schwann cells. • HGF induce c-Fos expression in SCs by ERK/CREB pathway. • c-Fos protein has role in various HGF-mediated responses in SCs. We previously reported that the expression of hepatocyte growth factor (HGF) was highly induced after peripheral nerve damage, and that c-Fos is one of many cellular genes whose expressions are affected by the increased level of HGF[1]. c-Fos is an important component of AP-1 heterodimer, but its role has not been clearly understood in the context of HGF and Schwann cells (SCs). In this study, we investigated the relationship between HGF and c-Fos. First, it was confirmed that the c-Fos was increased in SCs after nerve injury, while this effect abrogated by PHA-665752, an inhibitor of c-met receptor. When primary SCs were treated with recombinant HGF protein, c-Fos expression was regulated in a typical quick, transient fashion at both RNA and proteins levels. HGF-mediated induction of c-Fos expression was highly suppressed by specific inhibitors of ERK and CREB, respectively. The knock down of c-Fos expression by siRNA almost completely blocked various HGF-mediated effects in SCs, such as induction of gene expression of GDNF, LIF, and c-Myc, and migration of SCs, indicating that c-Fos might play a key role in HGF effects. Taken together, our results suggested that c-Fos plays a key role(s) in HGF-mediated effects on neurotrophic genes and cell migration.

• OSTI ID: 23103611
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GROWTH FACTORS
LIVER CELLS
RECEPTORS
RNA
SCIATIC NERVE