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

Experimental Dermatology
Jin Hee KimSang Wook Son

Abstract

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.

References

Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·V DrozdoffW J Pledger
Oct 31, 1998·Current Opinion in Genetics & Development·G L Semenza
Apr 25, 2001·The Journal of Biological Chemistry·S J D'SouzaL Dagnino
Jan 22, 2003·The Journal of Investigative Dermatology·Vladimir A Botchkarev
Jul 10, 2003·Cell Cycle·Richard A Woo, Randy Y C Poon
Aug 19, 2003·Nature Genetics·Sagrario OrtegaMariano Barbacid
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·Eleonora CandiGerry Melino
May 6, 2005·Cytokine & Growth Factor Reviews·Kohei MiyazonoTakeshi Imamura
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Xin-Hua Feng, Rik Derynck
Dec 3, 2005·Genes & Development·Joan MassaguéDavid Wotton
Jan 21, 2006·Birth Defects Research. Part C, Embryo Today : Reviews·Judith A MackEdward V Maytin
May 26, 2006·Nature·Jacques PouysségurNathalie M Mazure
Mar 9, 2007·International Journal of Dermatology·Laura E Tovar-CastilloMario E Cancino-Díaz
May 15, 2007·The Journal of Investigative Dermatology·Christian RosenbergerLawrence F Brown
Jul 31, 2007·Lancet·Christopher Em Griffiths, Jonathan Nwn Barker
Mar 8, 2008·The Journal of Investigative Dermatology·Carole PeyssonnauxRandall S Johnson
Jul 1, 2009·Journal of Cutaneous Pathology·Maria IoannouGeorge Koukoulis
Jun 3, 2011·The Journal of Investigative Dermatology·Hamid R RezvaniFrédéric Mazurier
Nov 8, 2011·Annual Review of Pathology·Gayathri K PereraFrank O Nestle
May 30, 2012·Journal of Cell Science·Suman K SinghDesmond J Tobin

❮ Previous
Next ❯

Citations

Aug 12, 2020·Experimental Dermatology·Stefania BrigantiMonica Ottaviani
May 7, 2020·Trends in Molecular Medicine·Danay CibrianFrancisco Sánchez-Madrid
Apr 13, 2021·Experimental Dermatology·Gina Pacella, Brian C Capell
May 21, 2021·PloS One·Sven OttoChristoph K W Mülling
Jun 26, 2020·International Immunopharmacology·Wen-Jing ZhuYang-Chun Xu
Sep 17, 2021·Communications Biology·Elena V KnatkoAlbena T Dinkova-Kostova

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.