p38 mitogen-activated protein kinase activation and cell localization in human glomerulonephritis: Correlation with renal injury
p38 mitogen-activated protein kinase activation and cell localization in human glomerulonephritis: Correlation with renal injury
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DOI：
10.1097/01.asn.0000108520.63445.e0
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发表时间：
2004-02-01
影响因子：
13.6
通讯作者：
Atkins, RC
中科院分区：
文献类型：
--
作者：
Stambe, C;Nikolic-Paterson, DJ;Atkins, RC
p38丝裂原活化蛋白激酶（MAPK）信号转导通路的激活在炎症反应中起重要作用。我们推测p38 MAPK在人肾小球肾炎的发病过程中起重要作用，并参与肾损伤的发展。通过免疫检测，我们检测了正常人类肾脏和77个肾活检标本中双磷酸化p38 （p-p38）的MAPK活化情况。在正常肾脏中，p-p38免疫染色仅限于少数足细胞、壁上皮细胞和小管细胞的细胞核。非增殖性和增殖性肾小球肾炎肾小球和小管中p-p38阳性细胞数量显著增加，增殖性肾小球肾炎间质中p-p38阳性细胞数量显著增加。双重免疫染色发现p38在内在肾细胞（足细胞、内皮细胞和肾小管细胞）、浸润性巨噬细胞和中性粒细胞以及肌成纤维细胞中活化。肾衰竭与p-p38阳性肾小球、小管和间质细胞的数量相关。非增殖性肾小球肾炎患者蛋白尿与p-p38阳性小管细胞和间质细胞数量以及p-p38阳性足细胞数量相关。此外，肾小球p38激活与节段性增生性和坏死性病变相关，间质p38激活与间质炎症程度相关。综上所述，p38 MAPK在肾细胞和浸润性白细胞中的激活与肾功能障碍和组织病理学相关，提示p38 MAPK激活在人肾小球肾炎中具有重要的致病作用。
Activation of the p38 mitogen-activated protein kinase (MAPK) signal transduction pathway plays an important role in the inflammatory response. It was postulated that p38 MAPK is important in the pathogenesis of human glomerulonephritis and contributes to the development of renal injury. p38 MAPK activation was examined by immunodetection for dual phosphorylated p38 (p-p38) in normal human kidney and 77 renal biopsy specimens encompassing a wide spectrum of glomerulonephritides. In normal kidney, p-p38 immunostaining was restricted to the nuclei of a small number of podocytes, parietal epithelial cells, and tubular cells. There was a dramatic increase in the number of p-p38-positive cells in glomeruli and tubules in nonproliferative and proliferative glomerulonephritis and a substantial increase in the number of interstitial p-p38-positive cells in proliferative glomerulonephritis. Double immunostaining identified p38 activation in intrinsic renal cells (podocytes and endothelial and tubular cells), infiltrating macrophage and neutrophils, and myofibroblasts. Renal failure correlated with the number of p-p38-positive glomerular, tubular, and interstitial cells. Proteinuria correlated with the number of p-p38-positive tubular and interstitial cells and the number of p-p38-positive podocytes in nonproliferative glomerulonephritis. Furthermore, glomerular p38 activation correlated with segmental proliferative and necrotic lesions, and interstitial p38 activation correlated with the degree of interstitial inflammation. In conclusion, activation of p38 MAPK in intrinsic renal cells and infiltrating leukocytes correlated with renal dysfunction and histopathology, suggesting an important pathogenic role for p38 MAPK activation in human glomerulonephritis.