Journal of Clinical Investigation · 1993 · 532 citations · 20 references
MedicineNephrologyPathologyCell ProliferationRenal PathologyRenal PathophysiologyGlomerular DiseasesGlomerular InjuryGlomerular PathophysiologyGrowth Factor SignalingRenal DiseaseGrowth FactorsMesangial Cell ProliferationMesangial ExpansionMesangial ProliferationOverexpression ConstructsTargeted TransfectionTransfection ReagentsTransforming Growth Factor Beta Regulation
Glomerulosclerosis, a common final lesion of glomerular disease, involves mesangial proliferation and extracellular matrix expansion, and although TGF‑β and PDGF regulate ECM metabolism and mesenchymal proliferation, their direct roles in disease pathogenesis remain unclear. The study employed an in‑vivo transfection approach to selectively overexpress either TGF‑β or PDGF‑B in the rat kidney. Overexpression of either TGF‑β or PDGF‑B alone induced glomerulosclerosis, with TGF‑β driving extracellular matrix accumulation and PDGF‑B driving mesangial cell proliferation.
Glomerulosclerosis, a final common lesion of various glomerular diseases, is characterized by mesangial cell proliferation and extracellular matrix (ECM) expansion. TGF-beta and PDGF are known to play a critical role in the regulation of ECM metabolism and mesenchymal cell proliferation, respectively. However, there is little evidence to demonstrate the direct role of each of these growth factors in the pathogenesis of glomerulosclerosis. Using an in vivo transfection technique, we could realize the selective overexpression of single growth factor in the kidney. The introduction of either TGF-beta or PDGF-B gene alone into the kidney induced glomerulosclerosis, although the patterns of action of these growth factors were different; TGF-beta affected ECM accumulation rather than cell proliferation and PDGF affected the latter rather than the former.
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IgG1 plasmacytosis in interleukin 6 transgenic mice.
S Suematsu, T Matsuda, Katsuyuki Aozasa et al. · Proceedings of the National Academy of Sciences · 1989 · 594 citations · Full text
Seiya Okuda, Lucia R. Languino, Erkki Ruoslahti et al. · Journal of Clinical Investigation · 1990 · 549 citations · Full text
Medicine, Nephrology, Pathology +16