Transfer of a mutated gene encoding active transforming growth factor-β1 suppresses mitogenesis and IL-1 response in the glomerulus
| Autor: | Leon G. Fine, Hiroshi Kawachi, Burton S, Masanori Kitamura, Jennifer A. English |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Renal glomerulus medicine.medical_treatment Mitosis Biology urologic and male genital diseases Transforming Growth Factor beta Internal medicine medicine Animals RNA Messenger Cells Cultured Mesangial cell urogenital system Growth factor Genetic transfer Gene Transfer Techniques Metalloendopeptidases Glomerulonephritis Blotting Northern medicine.disease Rats Inbred F344 Glomerular Mesangium Rats Cell biology Endocrinology Nephrology Nephritis Ex vivo Interleukin-1 Transforming growth factor |
| Zdroj: | Kidney International. 48(6):1747-1757 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.1995.473 |
| Popis: | Transfer of a mutated gene encoding active transforming growth factor-β1 suppresses mitogenesis and IL-1 response in the glomerulus. Using in vivo gene transfer, we examined the anti-inflammatory potential of transforming growth factor-β1 (TGF-β1) in the renal glomerulus. TGF-β1 cDNA, modified to allow for secretion of the active form of TGF-β1, was introduced into cultured rat mesangial cells. The responses of the established transfectants were examined in culture. In vitro , the transduced mesangial cells showed a reduced mitogenic response to fetal calf serum and were insensitive to induction of matrix metalloproteinase-9 (MMP-9) by the proinflammatory cytokine IL-1β. To examine whether glomeruli which express active TGF-β1 in vivo are insensitive to these same stimuli, TGF-β transfectants were transferred into normal rat glomeruli via renal artery injection. After 24 hours, isolated glomeruli containing transfectants exhibited TGF-β bioactivity, a reduced mitogenic response, and repressed expression of MMP-9 in response to IL-1β. We further examined the responses of these chimeric glomeruli to an in vivo mitogenic stimulus by transferring TGF-β transfectants into glomeruli of kidneys one day after the induction of anti-Thy-1 nephritis. The mitogenic activity of isolated glomeruli was examined four days after the cell injection. Compared to unmodified or mock cell-containing glomeruli, the in vivo mitogenic activity of glomeruli containing TGF-β transfectants was significantly repressed. Furthermore, cellular outgrowth from nephritic glomeruli expressing active TGF-β1 was also suppressed ex vivo compared to controls. These data indicate that TGF-β1 inhibits mitogenesis and IL-1 response of the glomerulus and may, in part, act as a potential early suppressor of glomerular inflammation. |
| Databáze: | OpenAIRE |
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