RNA-binding protein HuR regulates translation of vitamin D receptor modulating rapid epithelial restitution after wounding.
Am J Physiol Cell Physiol
; 319(1): C208-C217, 2020 07 01.
Article
em En
| MEDLINE
| ID: mdl-32432928
ABSTRACT
Homeostasis of the intestinal epithelium is tightly regulated by numerous extracellular and intracellular factors including vitamin D and the vitamin D receptor (VDR). VDR is highly expressed in the intestinal epithelium and is implicated in many aspects of gut mucosal pathophysiology, but the exact mechanism that controls VDR expression remains largely unknown. The RNA-binding protein human antigen R (HuR) regulates the stability and translation of target mRNAs and thus modulates various cellular processes and functions. Here we report a novel role of HuR in the posttranscriptional control of VDR expression in the intestinal epithelium. The levels of VDR in the intestinal mucosa decreased significantly in mice with ablated HuR, compared with control mice. HuR silencing in cultured intestinal epithelial cells (IECs) also reduced VDR levels, whereas HuR overexpression increased VDR abundance; neither intervention changed cellular Vdr mRNA content. Mechanistically, HuR bound to Vdr mRNA via its 3'-untranslated region (UTR) and enhanced VDR translation in IECs. Moreover, VDR silencing not only inhibited IEC migration over the wounded area in control cells but also prevented the increased migration in cells overexpressing HuR, although it did not alter IEC proliferation in vitro and growth of intestinal organoids ex vivo. The human intestinal mucosa from patients with inflammatory bowel diseases exhibited decreased levels of both HuR and VDR. These results indicate that HuR enhances VDR translation by directly interacting with its mRNA via 3'-UTR and that induced VDR by HuR is crucial for rapid intestinal epithelial restitution after wounding.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
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Receptores de Calcitriol
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Células Epiteliais
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Proteína Semelhante a ELAV 1
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Mucosa Intestinal
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article