Enhanced BMP signaling through ALK2 attenuates keratinocyte differentiation.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Activin Receptors, Type I*/genetics ; Activin Receptors, Type I*/metabolism ; Bone Morphogenetic Proteins*/metabolism; Animals ; Bone Morphogenetic Protein Receptors, Type I/genetics ; Bone Morphogenetic Protein Receptors, Type I/metabolism ; Cell Differentiation/genetics ; Keratinocytes/metabolism ; Mice ; Signal Transduction/genetics
    • Abstract:
      Accumulated studies have suggested that bone morphogenetic proteins (BMPs) are critical for skin development. However, it remains elusive how BMP signaling via ALK2 (aka ACVR1), one of the important BMP type I receptors, regulates keratinocyte differentiation. To address this question, we utilized a genetic system that enhances BMP signaling via ALK2 in an epidermis-specific manner in mice (hereafter ca-Alk2:K14-Cre). Ca-Alk2:K14-Cre mice displayed a sticky and hairless skin phenotype with a thinner epidermis incapable of differentiating. Although cellular proliferation and survival were comparable between wild-type and ca-Alk2:K14-Cre mice, skin differentiation was severely hampered in ca-Alk2:K14-Cre mice. To uncover the mechanism of altered keratinocyte differentiation, we performed a transcriptome analysis. As a result, we found that the expression levels of cell cycle inhibitor p21 were increased in ca-Alk2:K14-Cre mice. Our findings suggest that aberrant BMP signaling via ALK2 positively regulates p21 expression that attenuates keratinocyte differentiation, and further highlights the critical role of BMP signaling in skin development.
      (Copyright © 2022 Elsevier Inc. All rights reserved.)
    • Grant Information:
      R00 DE021054 United States DE NIDCR NIH HHS; R01 DE025897 United States DE NIDCR NIH HHS
    • Contributed Indexing:
      Keywords: ALK2; BMP signaling; Mouse; Skin; p21
    • Accession Number:
      0 (Bone Morphogenetic Proteins)
      EC 2.7.11.30 (Activin Receptors, Type I)
      EC 2.7.11.30 (Acvr1 protein, mouse)
      EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type I)
    • Publication Date:
      Date Created: 20220918 Date Completed: 20221004 Latest Revision: 20221020
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbrc.2022.09.014
    • Accession Number:
      36116371