Control of keratin gene expression by vitamin A in tracheobronchial epithelial cells.

T. H. Huang, D. K. Ann, Y. J. Zhang, A. T. Chang, J. W. Crabb, R. Wu

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Vitamin A (retinol) treatment induces (and/or enhances) mucous cell differentiation and alters keratin gene expression in cultured airway epithelial cells of human and nonhuman primate origin. We observed that retinol greatly reduced the synthesis of keratins 5, 6, 14, 16, and 17, but slightly enhanced keratins 7, 8, 10, 13, 15, 18, and 19. These changes were also reflected at the mRNA level as demonstrated by cell-free translation and by cDNA cloning of human keratin genes based on differential hybridization. One of these cDNA clones, HT27, isolated from the cDNA library of human tracheobronchial epithelial cells and whose expression in cultured cells was greatly suppressed by retinol, had a nucleotide sequence identical to the C-terminus of keratin 16. The identity of this clone was further confirmed by Western blot analysis using an antibody specific to the 15-amino acid synthetic peptide and the C-terminal sequence. Using this cDNA clone and two known keratin clones, pKA1 (keratins 5 and 6) and pKB2 (keratin 14), we found the levels of these corresponding mRNAs in cultured cells to be reduced 10- to 25-fold after treatment of cells with vitamin A. The inhibition was time- and dose-dependent with respect to retinol and was sensitive to prior treatment with cycloheximide. However, nuclear run-on transcriptional assays revealed no significant reduction of the synthesis of these messages in retinol-treated cultures. Furthermore, no change in the half-life of these mRNAs was observed in cells after the retinol treatment. Based on these results, we conclude that vitamin A indirectly controls the synthesis of these keratins at the post-transcriptional level.

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number2
StatePublished - Feb 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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