TY - JOUR
T1 - Signaling pathway by which TGF-β1 increases expression of latent TGF-β binding protein-2 at the transcriptional level
AU - Ahmed, Waseem
AU - Kucich, Umberto
AU - Abrams, William
AU - Bashir, Muhammad
AU - Rosenbloom, Joan
AU - Segade, Fernando
AU - Mecham, Robert
AU - Rosenbloom, Joel
N1 - Funding Information:
The excellent technical assistance of Gloria Shen is gratefully acknowledged. This work was supported by National Institutes of Health Grants HL56401 and AR41474.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - Elastin
KW - Gene transcription
KW - Latent transforming growth factor-β binding proteins
KW - Protein kinase C
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=0031734671&partnerID=8YFLogxK
U2 - 10.3109/03008209809002444
DO - 10.3109/03008209809002444
M3 - Article
C2 - 9862226
AN - SCOPUS:0031734671
VL - 37
SP - 263
EP - 276
JO - Connective Tissue Research
JF - Connective Tissue Research
SN - 0300-8207
IS - 3-4
ER -