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
APA
Chicago
ICMJE
MLA
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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.
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