ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue

Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demons...

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Detalles Bibliográficos
Autores principales: Kim, Min, Neinast, Michael D., Frank, Aaron P., Sun, Kai, Park, Jiyoung, Zehr, Jordan A., Vishvanath, Lavanya, Morselli, Eugenia, Amelotte, Mason, Palmer, Biff F., Gupta, Rana K., Scherer, Philipp E., Clegg, Deborah J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142394/
https://www.ncbi.nlm.nih.gov/pubmed/25161887
http://dx.doi.org/10.1016/j.molmet.2014.05.007
Descripción
Sumario:Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demonstrate HIF-1α is ubiquitinated following 17-β estradiol (E2)/ERα mediated Phd3 transcription. Manipulating ERα in vivo increases Phd3 transcription and reduces HIF-1 activity, while addition of PHD3 ameliorates adipose tissue fibrosis and inflammation. Our findings outline a novel regulatory relationship between E2/ERα, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ERα in adipose tissue.

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