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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kim, M; Neinast, MD; Frank, AP; Sun, K; Park, J; Zehr, JA; Vishvanath, L; Morselli, E; Amelotte, M; Palmer, BF; Gupta, RK; Scherer, PE; Clegg, DJ

Published Date

  • September 2014

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 642 - 651

PubMed ID

  • 25161887

Pubmed Central ID

  • PMC4142394

International Standard Serial Number (ISSN)

  • 2212-8778

Digital Object Identifier (DOI)

  • 10.1016/j.molmet.2014.05.007


  • eng

Conference Location

  • Germany