Signaling pathway by which TGF-β1 increases expression of latent TGF-β binding protein-2 at the transcriptional level

Waseem Ahmed, Umberto Kucich, William Abrams, Muhammad Bashir, Joan Rosenbloom, Fernando Segade, Robert Mecham, Joel Rosenbloom

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25 Scopus citations


The cytokine transforming growth factor-β has multiple effects on a wide variety of cell types. These effects include modulation of growth and regulation of gene transcription. In the present work, we demonstrate that TGF-β1 increases transcription of the latent transforming growth factor-β binding protein-2 (LTBP-2) gene in cultured human fetal lung fibroblasts leading to a significant increase in LTBP-2 mRNA steady state level. The stability of LTBP-2 mRNA was not appreciably altered. A corresponding increase in production of LTBP-2 protein accompanied the increase in mRNA. Through the use of specific inhibitors, we demonstrate that a member of the Ras super family and a protein kinase C, probably of the atypical (non-diacylglycerol, non-Ca++ dependent) class are likely to be components in the signaling pathway. However, phospholipases, G proteins and extracellular-signal regulated kinases do not appear to be involved. These results combined with previous findings on elastin regulation by TGF-β1 (Kucich et al. (1997). Am. J. Respir. Cell Mol. Biol., 17: 10-16) demonstrate that TGF-β1 can coordinately increase the steady state levels of mRNAs encoding components of the elastic fiber, but through diverse mechanisms. In contrast to LTBP-2, increased elastin expression is achieved by message stabilization. Furthermore, the TGF-β1 signaling pathways differ and while the pathway leading to increased LTBP-2 transcription shares components with those modulating transcription of other genes, it is unlikely to be precisely congruent with any other previously described one.

Original languageEnglish
Pages (from-to)263-276
Number of pages14
JournalConnective Tissue Research
Issue number3-4
StatePublished - 1998


  • Elastin
  • Gene transcription
  • Latent transforming growth factor-β binding proteins
  • Protein kinase C
  • Transforming growth factor-β


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