Abstract
We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen (COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF- stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti- TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10-7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS- stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.
Original language | English (US) |
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Pages (from-to) | F252-F258 |
Journal | American Journal of Physiology - Renal Physiology |
Volume | 274 |
Issue number | 2 43-2 |
DOIs | |
State | Published - Feb 1998 |
Keywords
- Estrogen
- Mesangial cells
- Mesangial matrix
- Sex hormones
- Transforming growth factor-β
ASJC Scopus subject areas
- Physiology
- Urology