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Search: WFRF:(Kobayashi Hirofumi) > (2019) > The ALK-1/SMAD/ATOH...

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  • Morikawa, MasatoUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Univ Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan (author)

The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • American Association for the Advancement of Science,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-398565
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-398565URI
  • https://doi.org/10.1126/scisignal.aay4430DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation-like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2 alpha (HIF-2 alpha) and decreased its abundance, leading to reduced induction of HIF-2 alpha target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.

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  • Mitani, YoshihideMie Univ, Grad Sch Med, Dept Pediat, Tsu, Mie 5148507, Japan (author)
  • Holmborn, KatarinaUppsala universitet,Science for Life Laboratory, SciLifeLab(Swepub:uu)kho01248 (author)
  • Kato, TaichiMie Univ, Grad Sch Med, Dept Pediat, Tsu, Mie 5148507, Japan;Nagoya Univ, Grad Sch Med, Dept Pediat Dev Pediat, Nagoya, Aichi 4668550, Japan (author)
  • Koinuma, DaizoUniv Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan (author)
  • Maruyama, JunkoMie Univ, Grad Sch Med, Dept Anesthesiol, Tsu, Mie 5148507, Japan;Suzuka Univ Med Sci, Fac Med Engn, Suzuka, Mie 5100293, Japan (author)
  • Vasilaki, EleftheriaUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)eleva536 (author)
  • Sawada, HirofumiMie Univ, Grad Sch Med, Dept Pediat, Tsu, Mie 5148507, Japan;Mie Univ, Grad Sch Med, Dept Anesthesiol, Tsu, Mie 5148507, Japan (author)
  • Kobayashi, MaiUniv Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan (author)
  • Ozawa, TakayukiUniv Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan (author)
  • Morishita, YasuyukiUniv Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan (author)
  • Bessho, YasumasaKyoto Univ, Inst Frontier Life & Med Sci, Sakyo Ku, Kyoto 6068507, Japan;Nara Inst Sci & Technol NAIST, Grad Sch Biol Sci, Dept Syst Biol, Nara 6300101, Japan (author)
  • Maeda, ShingoKagoshima Univ, Dept Med Joint Mat, Kagoshima, Kagoshima 8908544, Japan (author)
  • Ledin, JohanUppsala universitet,Science for Life Laboratory, SciLifeLab(Swepub:uu)joled677 (author)
  • Aburatani, HiroyukiUniv Tokyo, RCAST, Genome Sci Div, Meguro Ku, Tokyo 1538904, Japan (author)
  • Kageyama, RyoichiroKyoto Univ, Inst Frontier Life & Med Sci, Sakyo Ku, Kyoto 6068507, Japan (author)
  • Maruyama, KazuoMie Univ, Grad Sch Med, Dept Anesthesiol, Tsu, Mie 5148507, Japan (author)
  • Heldin, Carl-Henrik,1952-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)carlheld (author)
  • Miyazono, KoheiUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Univ Tokyo, Grad Sch Med, Dept Mol Med, Bunkyo Ku, Tokyo 1130033, Japan(Swepub:uu)komiy676 (author)
  • Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Related titles

  • In:Science Signaling: American Association for the Advancement of Science12:6071945-08771937-9145

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