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Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients.

Takahashi T, Shirasawa T, Miyake K, Yahagi Y, Matsumura O, Abe A, Natori Y, Yamabe H, Utsunomiya Y, Maruyama N, Mitarai T, Sakai O
Clin Exp Immunol. 1996 104 (3): 517-24

PMID: 9099938 · PMCID: PMC2200441 · DOI:10.1046/j.1365-2249.1996.62768.x

Jak3 is a member of the Janus kinase family which plays an important role in cytokine signal transduction. Jak3 associates the gamma(c) chain of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15, and is essential for the signal transduction of these cytokines. We have isolated Jak3 kinase from renal mesangial cells and demonstrated the constitutive expression of Jak3 in glomeruli in vivo. To investigate the physiological and pathological role of Jak3 in glomeruli, we prepared anti-Jak3 antibody and analysed the localization of Jak3 in glomeruli of renal biopsy samples from various nephritis patients and normal subjects. Among 61 nephritis patients and four normal subjects investigated in the present study, Jak3 was selectively localized to glomerular epithelia of IgA-N patients (14/34 cases) and focal glomerulosclerosis patients (1/5 cases), but not detected in minimal changes (n = 6), membranous glomerulonephropathy (n = 7), crescentic glomerulonephritis (n = 4), lupus nephritis patients (n = 5), and normal subjects (n = 4). The intense immunoreactivity for Jak3 is significantly associated with the decrease in creatinine clearance (81.5 +/- 10.4 ml/min versus 104.3 +/- 29.6 ml/min; P < 0.05, Student's t-test) and the increase in level of serum creatinine (1.13 +/- 0.33 mg/dl versus 0.75 +/- 0.23 mg/dl; P < 0.01, Student's t-test) in IgA-N patients. Furthermore, gamma(c) chain was concomitantly expressed with Jak3 in glomerular epithelia in vivo and in vitro, suggesting that signal transduction via gamma(c)-Jak3 cascade may be involved in the pathogenesis of glomerular injury of IgA-N. Taken together with the recent findings that IL-4-secreting T lymphocytes in affected glomeruli injure glomerular epithelium, the responsiveness of glomerular epithelium for IL-4 may be pathologically enhanced in IgA-N.

MeSH Terms (28)

Animals Biopsy Blotting, Northern Cells, Cultured Creatinine Electrophoresis, Polyacrylamide Gel Epithelium Gene Expression Regulation Glomerulonephritis Glomerulonephritis, IGA Glomerulonephritis, Membranous Glomerulosclerosis, Focal Segmental Humans Immunohistochemistry Janus Kinase 3 Kidney Kidney Glomerulus Lupus Nephritis Polymerase Chain Reaction Precipitin Tests Protein-Tyrosine Kinases Protein Biosynthesis Rats Recombinant Proteins Recombination, Genetic RNA Sensitivity and Specificity Signal Transduction

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