TGF-β-like Transcriptional Effects of Thyroglobulin (Tg) in Mouse Mesangial Cells

Endocrine Journal

Claudia LAGRANHA¹  Donald F. SELLITTI⁴  Leonard D. KOHN³  Koichi SUZUKI²  Sonia Q. DOI⁴  Enrico PUGGINA¹  Tania PITHON-CURI¹ 

[1] University of Sao Paulo;Leprosy Research Center, National Institute of Infectious Diseases;Edison Biotechnology Institute and College of Osteopathic Medicine, Ohio University;Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD

关键词: TGF-β1;    thyroglobulin;    mesangial cells;    Pax-8;    PAI-1;   

DOI  :  10.1507/endocrj.K06-178

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(34)Cited-By(7)TGF-β-like activities of proteins unrelated to the cytokine could mimic its actions in fibrosis and cell proliferation. Thyroglobulin (Tg) has been identified as having a TGF-β receptor (TGFβR)-binding activity and is deposited in the glomerulus in certain immune-complex diseases. The aim of the present study is to determine whether Tg can reproduce the transcriptional activity of TGF-β1 in the mouse glomerular mesangial cell (MC), and to examine whether such activity is manifested through TGFβR. Real-time RT-PCR was employed to examine the effects of TGF-β1 and bovine Tg on the expression of three genes (TGF-β1, plasminogen activator inhibitor 1 [PAI-1], and Pax-8) regulated by TGF-β1 in other cell types. In addition, a pentacosapeptide TGF-β1 antagonist, β125 (41-65) was employed to determine whether the transcriptional activity of Tg was mediated through the TGF-β binding site on the TGFβR. A 6h exposure to TGF-β1 resulted in increased TGF-β1 and PAI-1 transcript, and a decrease in Pax-8. Similarly, a 6h exposure to Tg resulted in increases of about 5-fold in TGF-β1 and PAI-1 mRNA and a decrease of 53% in Pax-8. In comparison with other proteins, Tg had the greatest positive effect on TGF-β1 transcript levels. β125 (41-65) significantly reduced the TGF-β1-, but not the Tg-induced changes in TGF-β1, PAI-1 and Pax-8 transcript levels. We conclude from these studies that Tg possesses a TGF-β-mimetic transcriptional activity in the MC that is not mediated by its binding to TGFβR. These results suggest that Tg and other proteins could initiate glomerular injury by reproducing the actions of TGF-β1 in the mesangial cell.

【 授权许可】

Unknown