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ERK2 but not ERK1 plays a key role in hepatocyte replication: an RNAi-mediated ERK2 knockdown approach in wild-type and ERK1 null hepatocytes

Frémin, Christophe, Ezan, Frédéric, Boisselier, Pierre, Bessard, Anne, Pagès, Gilles, Pouysségur, Jacques, Baffet, Georges·2007·Hepatology
DOI 10.1002/hep.21551
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Abstract

Unlabelled The mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 have been implicated in various physiological events, and specific targeting of these MAPKs could affect cell proliferation in many cell types. First, to evaluate the potential specific roles of these two MAPKs, we analyzed the mitogenic response in regenerating liver after partial hepatectomy (PH) and in primary culture of hepatocytes isolated from ERK1-deficient mice. We show that ERK1 knockout and wild-type (wt) cells replicate with the same kinetics after PH in liver, in vivo, and in primary cultures of hepatocytes, in vitro. Indeed, Cyclin D1 and Cdk1 appear to be expressed concomitantly in knockout and wt cells, highlighting that hepatocytes progress in the cell cycle independently of the presence of ERK1. Second, we specifically abolished ERK2 expression by RNA interference in mouse and rat hepatocytes. We investigated whether small interfering RNA (siRNA) targeting ERK2 could specifically inhibit its expression and interfere with the process of replication. In ERK1-deficient hepatocytes, silencing ERK2 expression by RNA interference and ERK2 activation by U0126 clearly demonstrate that DNA replication is regulated by an ERK2-dependent mechanism. Furthermore, in rat wt hepatocytes, whereas ERK2 targeting inhibits late G(1) and S phase progression, ERK1 silencing is devoid of any effect on cell proliferation, indicating that ERK1 cannot rescue ERK2 deficiency. Conclusion Our results emphasize the imp…

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  • In hepatocytes, many hormones and growth factors such as EGF and FGF stimulate ERK1/2 signaling.

    “In hepatocytes, many hormones and growth factors such as epidermal growth factors (EGF) and fibroblast growth factors (FGF) are able to stimulate ERK1/2 signaling cascade (Fremin et al., 2007; Guegan et al., 2012).”

    From GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis (2019) · cites this paper as Fremin et al., 2007

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Metadata

Authors
Frémin, C., Ezan, F., Boisselier, P., Bessard, A., Pagès, G., Pouysségur, J., & Baffet, G.
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2007-04
Volume
45
Issue
4
Pages
1035-1045
ISSN
0270-9139
DOI
10.1002/hep.21551
Cited by
99
References
3
Language
en
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3075 d)

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