| Exp Cell Res. 1995 Dec;221(2):385-94. |
|
Differential modulation
of integrin receptors and extracellular
matrix laminin by transforming growth factor-beta
1 in rat alveolar epithelial cells.
Kumar NM, Sigurdson SL, Sheppard D, Lwebuga-Mukasa JS.
Department of Internal Medicine, SUNY
at Buffalo School of Medicine, Buffalo General Hospital
14203,
The transforming growth factors-beta (TGFs-beta)
family of genes plays important roles in cell growth and differentiation in
many cell types. TGF beta modulates the synthesis
and accumulation of extracellular matrix (ECM) components and the expression of cell surface receptors
for ECM components. TGF
beta is increased in alveolar lining fluid during inflammatory reactions of
the lung and has been identified in alveolar epithelial cells of developing
lungs and hyperplastic type II cells during repair.
However, little is known about how TGF beta may
regulate expression of extracellular matrix proteins
and ECM receptors in lung alveolar epithelial cells.
Laminin, a major glycoprotein component of epithelial basement
membrane, is synthesized and secreted by alveolar epithelial cells. To study
the effects of TGF beta on modulation of laminin and its integrin receptors
alpha 6 beta 1 and alpha 3 beta 1 in lung alveolar epithelial cells, a rat
alveolar type II cell-derived cell line, LM5, was
incubated with TGF beta 1 (0-100 pg/ml) in serum-free
medium for 0-16 h. We examined the expression of integrin
subunits and laminin beta 2 chain (s-laminin) mRNAs and protein expression. By Northern blot analysis, TGF beta 1 induced dose-dependent
increases in alpha 6 and beta 1 mRNA levels. TGF
beta 1 also increased the expression of laminin
beta 2 chain mRNA at 12-16 h poststimulation. In
contrast, TGF beta 1 decreased alpha 3
mRNA expression. Immunoprecipitation studies of
TGF beta 1-treated cells showed increased surface expression
of both alpha 6 and beta 1 protein while surface expression of the alpha 3
integrin subunit was decreased. The same treatment
resulted in increased laminin protein expression.
These data suggest that TGF beta 1 may regulate
alveolar epithelial cell differentiation in part through its modulation of
integrins and laminin
chains.
PMID: 7493638 [PubMed
- indexed for MEDLINE]