Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-β-mediated epidermal homeostasis

Yoshihiro Ito, Partha Sarkar, Qingli Mi, Nancy Wu, Pablo Bringas, Yihsin Liu, Sita Reddy, Robert Maxson, Chuxia Deng, Yang Chai

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Members of the transforming growth factor-β (TGF-β) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-β signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-β and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-β1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-β signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-β signaling, Smad2 plays a pivotal role in regulating TGF-β-mediated epidermal homeostasis.

Original languageEnglish (US)
Pages (from-to)181-194
Number of pages14
JournalDevelopmental Biology
Volume236
Issue number1
DOIs
StatePublished - Aug 1 2001
Externally publishedYes

Keywords

  • Skin
  • Smad2 transgenic
  • Smad4
  • TGF-β signaling
  • Tooth

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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