当前位置： SCI文献检索 > MOLECULAR AND CELLULAR ENDOCRINOLOGY期刊下所有文献 > Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization.

Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization.

Abstract：

:Activation of mineralocorticoid receptor (MR) is evoked by aldosterone, and it induces hypertension and cardiovascular disease when it's concomitant with excessive salt loading. We have proposed the notion of "MR-associated hypertension", in which add-on therapy of MR blockers is effective even though serum aldosterone level is within normal range. To elucidate its underlying molecular mechanism, we focused on the effect of epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) activation on MR activity. Epidermal growth factor (EGF) administration increased MR transcriptional activity through EGFR/ERK pathway and increased protein level by counteracting MR ubiquitylation in vitro. EGF administration in vivo also increased MR protein level and target gene expression in kidney, which were decreased by EGFR inhibitor. In addition, the administration of EGFR inhibitor lowered systolic blood pressure and MR activity in DOCA/salt-treated mice. In conclusion, EGFR/ERK pathway activation is considered as one of the underlying mechanisms of aberrant MR activation and EGFR/ERK pathway blockade could be an alternative approach for the prevention of MR-related cardiovascular events.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Mitsuishi Y,Shibata H,Kurihara I,Kobayashi S,Yokota K,Murai-Takeda A,Hayashi T,Jo R,Nakamura T,Morisaki M,Itoh H

doi

10.1016/j.mce.2018.01.007

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

89-99

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(18)30017-0

journal_volume

473

pub_type

杂志文章

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