INCREASED MESSENGER-RNA ENCODING FOR TRANSFORMING FACTOR-BETA IN CD4+ CELLS FROM PATIENTS WITH IGA NEPHROPATHY
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AbstractIgA nephropathy (IgAN) is a mesangial proliferative glomerulonephritis characterized by predominant mesangial IgA deposits. Recently, transforming growth factor-beta (TGF-beta) is shown to exert widespread effects on extracellular matrix by enhancing its accumulation. In an experimental model of acute mesangial glomerulonephritis TGF-beta appeared to be involved in the process of glomerulosclerosis, and treatment with antagonists of TGF-beta prevented the development of glomerulosclerosis. We examined the TGF-beta mRNA expression by mitogen activated CD4+ T cells from 31 patients with IgAN, 25 healthy controls and 10 patients with minimal change nephropathy (MCN) or focal glomerulonephritis (FGN) who were comparable in age and sex. The cytokine gene was analyzed with reverse transcription followed by polymerase chain reaction and was semiquantitated by normalizing the differences occurring during reverse transcription and polymerase chain reaction using a housekeeping gene, beta-actin. CD4+ T cells from IgA nephritic patients expressed a higher level of TGF-beta mRNA than that of healthy controls or that of MCN/FGN [TGF-beta/actin ratio 1.11 (median), range 0.24 to 3.87 vs. 0.88, range 0.2 to 3.83, P = 0.0157 and 0.36 range 0.09 to 1.6, P = 0.006]. When the biopsies were classified into three grades according to the severity of glomerular and interstitial pathology, there were highly significant differences between the TGF-beta mRNA in CD4+ T cells from the three groups of IgA nephritic patients (grade 1, 0.52, range 0.24 to 0.79; grade 2, 1.2, range 0.5 to 3.33; grade 3, 2.17, range 1.45 to 3.87]. Furthermore, immunofluorescent reactivity of anti-TGF-beta antibody in the mesangium was associated with the severity of histopathologic grading (P < 0.05). Our data suggest that, in addition to the local synthesis of TGF-beta by mesangial cells, there is increased TGF-beta gene expression in circulating CD4+ T cells that may also contribute to the glomerulosclerosis in IgA nephropathy.
All Author(s) ListLAI KN, HO RTH, LEUNG JCK, LAI FMM, LI PKT
Journal nameKidney International
Year1994
Month9
Day1
Volume Number46
Issue Number3
PublisherNATURE PUBLISHING GROUP
Pages862 - 868
ISSN0085-2538
eISSN1523-1755
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesUrology & Nephrology; UROLOGY & NEPHROLOGY

Last updated on 2020-03-08 at 06:17