Effect of transforming growth factor-beta on extracellular matrix production by cultured rat mesangial cells.
The effects of transforming growth factor-beta (TGF-beta) on the protein synthesis and gene expression of collagen I (CI), III (CIII), IV (CIV) and laminin (LM) in cultured rat mesangial cells (MCs) were examined to determine whether or not TGF-beta could modulate the formation of extracellular matrix (ECM) constituents, employing immunocytochemistry, enzyme-linked immunoadsorbent assay (ELISA) and Northern blotting. Although TGF-beta did not modulate MC proliferation, it induced slight enhancement of immunoperoxidase staining for CIV in the cytoplasm. ELISA demonstrated a significant increase in the amounts of CIV and LM, a tendency for CIII to increase, and a significantly lower amount of CI at 4 days after TGF-beta administration. Northern blotting showed that the mRNA expression displayed different patterns among the 4 matrix components during a 24-hr period. These findings suggest that a single growth factor, TGF-beta, in vitro modulates the synthesis of individual ECM constituents in MCs differently at the level of both genetic expression and protein production. The specific effects of TGF-beta on the increase in amounts of CIV and LM indicate that TGF-beta may contribute to glomerular remodeling and ECM accumulation in various kinds of glomerular injuries.
Ishimura
E
E
Department of Medicine, Yale University School of Medicine, New Haven, Con.
Morii
H
H
Sterzel
R B
RB
Kashgarian
M
M
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007797:Laminin / Q000096:biosynthesis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D007797:Laminin; D016212:Transforming Growth Factor beta; D003094:Collagen