Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys.

作者：Kazuo Yoshioka, Tamiko Takemura, Katsumi Murakami, Morihito Okada, Shinjiro Hino, Hiroyuki Miyamoto, S. Maki · 发表于：PubMed · 年份：1993 · 被引用次数：251 · 研究领域：Chronic Kidney Disease and Diabetes、TGF-β signaling in diseases、Renal Diseases and Glomerulopathies

BACKGROUND: Evidence indicates a key role for transforming growth factor-beta (TGF-beta) in the accumulation of pathologic extracellular matrix in experimental glomerular injury. The aim of this study was to elucidate the expression of TGF-beta and its role in human glomerulonephritis. EXPERIMENTAL DESIGN: Expression of TGF-beta 1 in normal and diseased human kidneys was examined by immunohistochemical staining with two antibodies (Ab1 and Ab2), and by in situ hybridization with an oligonucleotide probe. RESULTS: Staining with Ab1, which mainly recognizes mature TGF-beta 1 and the latency-associated peptide (LAP) of natural TGF-beta 1, was linearly positive along the glomerular basement membrane (GBM) and weakly so in the mesangium of normal tissues and those of various glomerular diseases which were pretreated with acid-urea to unmask a hidden epitope. Ab2, which reacts mainly with TGF-beta-LAP, bound to the mesangium and sclerotic areas of the tissues untreated with acid-urea. Immunoelectron microscopy showed that Ab1 was localized to the GBM and the mesangial matrix, and that Ab2 was distributed in subepithelial, or mesangial/paramesangial electron-dense deposits. The presence of mature TGF-beta 1 and TGF-beta-LAP in normal kidneys was confirmed by immunoblotting using guanidine-extracted fractions of glomeruli and GBM isolated from normal human kidneys. Mesangial staining of TGF-beta 1 with Ab2 was significantly correlated with the mesangial matrix increase in mesangial p...