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MicroRNA‐21 Increases Aldosterone Secretion and Proliferation in H295R Human Adrenocortical Cells
Author(s) -
Romero Damian G.,
Plonczynski Maria W.,
Carvajal Cristian A.,
GomezSanchez Elise P.,
GomezSanchez Celso E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.736.6
Subject(s) - aldosterone , microrna , medicine , endocrinology , angiotensin ii , downregulation and upregulation , zona glomerulosa , biology , cell growth , adrenal cortex , secretion , adrenocortical carcinoma , gene , biochemistry , genetics , blood pressure
MicroRNAs (miRNAs) are endogenous small non‐coding RNAs which decrease the expression levels of specific genes by translational repression, sequestration and degradation of their mRNAs. Angiotensin II (AII) is an important modulator of adrenal zona glomerulosa steroidogenesis and proliferation. Since each miRNA may regulate the expression level of multiple genes, thereby resembling the mechanism of action and regulatory networks of transcription factors, we hypothesize that specific miRNAs may be involved in AII‐mediated adrenocortical cell responses. We screened more than 200 miRNAs for miRNAs regulated by AII in the human adrenocortical cell line H295R and found that mir‐21 expression levels were specifically and time dependently upregulated by AII reaching a 4.4‐fold (n=3, p<0.05) induction after 24 h. AII upregulated mir‐21 was biologically active as determined by its ability to decrease 40 % (n=6, p<0.05) the expression of a fusion mRNA reporter system with mir‐21 target sequences. Plasmid‐driven overexpression of mir‐21 increased aldosterone secretion (27.7(4.1 vs. 16.4(0.7 pg/(g prot.day, n=3, p<0.05), but not cortisol (226(26 vs. 218(13 pg/(g prot.day, n=3, p<0.05) and cell proliferation (132.6(1.5 vs. 100.0(6.0 % control, n=6, p<0.05). Alterations in mir‐21 expression levels or function may be involved in dysregulation of AII signaling and abnormal adrenal aldosterone secretion in humans