Evidence map›Paper›PMID 29295567›Full record

ArticleInternational journal of molecular sciences2017

Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase.

Soohwan Yum, Seongkeun Jeong, Dohoon Kim, Sunyoung Lee, Wooseong Kim, Jin-Wook Yoo, Jung-Ae Kim, Oh Sang Kwon, Dae-Duk Kim, Do Sik Min and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
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  8. The Extract ofCurrent issues in molecular biology · 2025
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  11. KyohMolecules (Basel, Switzerland) · 2025
    Article
  12. Review
  13. Review
  14. Hair Growth Effect and the Mechanisms ofInternational journal of molecular sciences · 2024
    Article
  15. [Conbercept reverses TGF-βNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
    Article
  16. Article
  17. Review
  18. Molecules (Basel, Switzerland) · 2024
    Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Soohwan YumCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. roy-yum@hanmail.net.
Seongkeun JeongCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. finesiecle@gmail.com.
Dohoon KimCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. gumx1234@gmail.com.
Sunyoung LeeCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. lsy123@nst.re.kr.
Wooseong KimCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. b04420@nate.com.
Jin-Wook YooCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. jinwook@pusan.ac.kr.
Jung-Ae KimCollege of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea. jakim@yu.ac.kr.ORCID 0000-0002-0824-8532
Oh Sang KwonDepartment of Dermatology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 110-744, Korea. oskwon@snu.ac.kr.
Dae-Duk KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea. ddkim@snu.ac.kr.
Do Sik MinDepartment of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735, Korea. minds@pusan.ac.kr.
Yunjin JungCollege of Pharmacy, Pusan National University, Busan 609-735, Korea. jungy@pusan.ac.kr.
Pusan National University · KRSeoul National University · KRSeoul National University Hospital · KRYeungnam University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF), a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF) prolyl hydroxylase-2 (PHD-2) was tested by an in vitro von Hippel-Lindau protein (VHL) binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM) assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α), and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1.

Indexed as

Ascorbic AcidChorioallantoic MembraneHumansHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesMinoxidilNeovascularization, PhysiologicSkinVascular Endothelial Growth Factor AAscorbic AcidHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesMinoxidilVascular Endothelial Growth Factor Aangiogenesishypoxia inducible factorminoxidilvascular endothelial growth factorvon Hippel–Lindau protein

Identifiers

PMID29295567
PMCPMC5796003
OpenAlexW2778732176

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.