HIF-1α-mediated BMP6 down-regulation leads to hyperproliferation and abnormal differentiation of keratinocytes in vitro

Jin Hee Kim, Hyun Cheol Bae, Jaehyung Kim, Hana Lee, Woo In Ryu, Eui Dong Son, Tae Ryong Lee, Sang Hoon Jeong, Sang Wook Son

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Hypoxia-inducible factor-1α (HIF-1α) has been reported to be up-regulated in psoriatic epidermis, resulting in increased proliferation and abnormal differentiation of human keratinocytes (KCs). However, the role of HIF-1α in psoriatic epidermis, which is mainly composed of KCs, is poorly understood. Here, we show that morphogenic protein 6 (BMP6) is down-regulated when HIF-1α is upregulated in patients with psoriasis skin lesions. HIF-1α overexpression in primary human KCs promoted proliferation and inhibited terminal differentiation. Furthermore, HIF1-α repressed the expression of BMP6 by binding directly to the hypoxia-response element (HRE) in the BMP6 promotor region, which shows that BMP6 is a novel target gene of HIF-1α. We also found that HIF-1α-mediated BMP6 suppression could alter the proliferation status by modulating the expression levels of cell cycle regulatory proteins and also affect the early differentiation of KCs. Therefore, we suggest that HIF-1α-dependent BMP6 suppression has a critical role in the induction of hyper-proliferation and abnormal differentiation in psoriatic KCs.

Original languageEnglish
Pages (from-to)1287-1293
Number of pages7
JournalExperimental Dermatology
Issue number11
Publication statusPublished - 2018 Nov

Bibliographical note

Funding Information:
This study was supported by a Korea University Grant, the Amorepacific Corporation and Basic Science Research Program through the National Research Foundation of Korea (NRF), and funded by the Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4016161).

Publisher Copyright:
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • BMP6
  • HIF-1α
  • keratinocyte
  • psoriasis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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