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

Publication ,  Journal Article
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 in: Mol Metab
September 2014

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.

Duke Scholars

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Published In

Mol Metab

DOI

ISSN

2212-8778

Publication Date

September 2014

Volume

3

Issue

6

Start / End Page

642 / 651

Location

Germany

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Chicago
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Kim, M., Neinast, M. D., Frank, A. P., Sun, K., Park, J., Zehr, J. A., … Clegg, D. J. (2014). ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue. Mol Metab, 3(6), 642–651. https://doi.org/10.1016/j.molmet.2014.05.007
Kim, Min, Michael D. Neinast, Aaron P. Frank, Kai Sun, Jiyoung Park, Jordan A. Zehr, Lavanya Vishvanath, et al. “ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue.Mol Metab 3, no. 6 (September 2014): 642–51. https://doi.org/10.1016/j.molmet.2014.05.007.
Kim M, Neinast MD, Frank AP, Sun K, Park J, Zehr JA, et al. ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue. Mol Metab. 2014 Sep;3(6):642–51.
Kim, Min, et al. “ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue.Mol Metab, vol. 3, no. 6, Sept. 2014, pp. 642–51. Pubmed, doi:10.1016/j.molmet.2014.05.007.
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. ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue. Mol Metab. 2014 Sep;3(6):642–651.
Journal cover image

Published In

Mol Metab

DOI

ISSN

2212-8778

Publication Date

September 2014

Volume

3

Issue

6

Start / End Page

642 / 651

Location

Germany

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology