Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1.
Central features of progressive glomerular sclerosis are initial glomerular hypertrophy and subsequent accumulation of extracellular matrix proteins. Since TGF-beta 1 may play a key role in this glomerular response to injury, the present study sought to explore further TGF-beta 1 actions and regulated expression of its receptor in rat mesangial cells. The rat TGF-beta type II receptor (TGF-beta RII) homolog was cloned by screening a rat kidney cDNA library with a human TGF-beta RII cDNA probe, and sequenced. Expression of this receptor subtype in rat mesangial cells was then demonstrated by RNase protection assay, and by Northern blot analysis of poly (A)+ RNA, TGF-beta RII expression was down-regulated in cells treated with exogenous TGF-beta 1. Affinity cross linking studies demonstrated presence of this receptor on cell surface. Rat mesangial cells also expressed TGF-beta 1 and autoinduction by TGF-beta 1 was observed in the same cells, suggesting that this polypeptide may act in an autocrine fashion on mesangial cells, and that it may stimulate a positive autoamplification loop. TGF-beta 1 inhibited mesangial cell proliferation and stimulated significant overall protein and collagen production. Furthermore, mesangial cell size increased in response to chronic TGF-beta 1 treatment. These findings demonstrate that rat mesangial cells express key components of the TGF-beta system and raise the intriguing possibility that in the glomerular mesangium, TGF-beta 1 may not only induce extracellular matrix synthesis, but may also participate in the process of glomerular hypertrophy in response to injury.
Choi
M E
ME
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kim
E G
EG
Huang
Q
Q
Ballermann
B J
BJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000473:pathology; D006984:Hypertrophy; D007930:Leucine / Q000378:metabolism; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D018076:DNA, Complementary; D015335:Molecular Probes; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D011392:Proline; D007930:Leucine; D013936:Thymidine