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p73 regulates epidermal wound healing and induced keratinocyte programming.
Beeler, J Scott; Marshall, Clayton B; Gonzalez-Ericsson, Paula I; Shaver, Timothy M; Santos Guasch, Gabriela L; Lea, Spencer T; Johnson, Kimberly N; Jin, Hailing; Venters, Bryan J; Sanders, Melinda E; Pietenpol, Jennifer A.
Afiliación
  • Beeler JS; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Marshall CB; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Gonzalez-Ericsson PI; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Shaver TM; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Santos Guasch GL; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Lea ST; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Johnson KN; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Jin H; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Venters BJ; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Sanders ME; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Pietenpol JA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One ; 14(6): e0218458, 2019.
Article en En | MEDLINE | ID: mdl-31216312
p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by ΔNp73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piel / Cicatrización de Heridas / Ectodermo / Proteína Tumoral p73 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piel / Cicatrización de Heridas / Ectodermo / Proteína Tumoral p73 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos