Jak Tyrosine Kinases in IgA Nephropathy

IgA 肾病中的 Jak 酪氨酸激酶

基本信息

批准号：
07671264
负责人：
SAKAI Osamu
金额：
$ 1.41万
依托单位：
The Jikei University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Jak3 is a member of Janus Kinase which play an important role in cytokine signal transductions. Jak3 associates gamma<@D2c@>D2 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 analyzed the localization of Jak3 in glomeruli of renal biopsy samples from various nephritis patients and normal subjects. Among 61 nephritis patients and 4 normal subjects investigated in the present study, Jak3 is selectively localized to glomerular epithelia of IgA nephropathy patients (14/34 cases) and focal glomerulosclerosis patients (1/5 cases), but not detected in minimal changes (6 cases), membranous glomerulonephropathy (7 cases), crescentic glomerulonephritis (4 cases), lupus nephritis patients (5 cases), and normal subjects (4 cases). The intense immunoreactivity for Jak3 is significantly associated with the decrease in creatinine clearance (81.5 (]SY+-[) 10.4 vs 104.3 (]SY+-[) 29.6ml/min, P<0.05, Student's t-test) and the increase in the level of serum creatinine (1.13 (]SY+-[) 0.33 vs 0.75 (]SY+-[) 0.23 mg/dl, P<0.01, Student's t-test) in IgA nephropathy patients. Furthermore, gamma<@D2c@>D2 chain was concomitantly expressed with Jak3 in glomerular epithelia in vivo and in vitro, suggesting that the signal transduction via gamma<@D2c@>D2-Jak3 cascade may be involved in the pathogenesis of glomerular injury of IgA nephropathy. 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 nephropathy.

JAK3是Janus激酶的成员，它在细胞因子信号转导中起重要作用。 JAK3将gamma <@d2c@> D2的受体链与IL-2，IL-4，IL-7，IL-9和IL-15相关联，对于这些细胞因子的信号转导至关重要。我们已经从肾小球细胞中分离出JAK3激酶，并证明了在体内肾小球中Jak3的组成型表达。为了研究JAK3在Glomeruli中的生理和病理作用，我们制备了抗JAK3抗体，并分析了JAK3在各种肾炎患者和正常受试者的肾脏活检样品肾小球中的定位。在本研究中调查的61名肾炎患者和4名正常受试者中，JAK3被选择性地定位于IgA肾病患者（14/34例）和局灶性肾小球硬膜病患者（1/5例）的肾小球上皮（1/5例），但在最小的变化中未检测到（6例），膜状Glomerulyphromerliry（7例）。（4例），狼疮肾炎患者（5例）和正常受试者（4例）。 JAK3的强烈免疫反应性与肌酐清除率的降低显着相关（81.5（] SY+ - [）10.4 vs 104.3（] SY+ - [）29.6ml/min，P <0.05，Student's T-test）和血清肌酐（SY.13（SY+ - ] 0.33 Vs+ - [1.33 vs）的水平增加IgA肾病患者中的Mg/dl，p <0.01，Student t-test）。此外，伽马<@d2c@> d2链在体内和体外与Jak3同时表达，表明通过gamma <@d2c@> d2c@> d2-jak3 cascade信号转导的信号转导可能涉及glomerulular损伤Inphropaty的病原体。总而言之，最近发现的IL-4分泌T淋巴细胞在受影响的肾小球损伤肾小球上皮中，IGA肾病中IGA肾小球上皮对IL-4的反应性可能会在病理上增强。