Up regulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in primary glomerular diseases: a possible involvement of the ER stress pathway in glomerulonephritis

Up regulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in primary glomerular diseases: a possible involvement of the ER stress pathway in glomerulonephritis
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DOI:
10.1007/s11010-008-9991-2
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发表时间:
2009-04-01
影响因子:
4.3
通讯作者:
Khullar, Madhu
Khullar, Madhu
中科院分区:
生物学3区
文献类型:
--
作者:
Markan, Suchita;Kohli, Harbir Singh;Khullar, Madhu

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内质网应激在肾脏疾病中的作用尚未得到很好的阐明。入选原发性肾小球疾病(PGD)患者50例:微小病变病(MCD)、局灶节段性肾小球硬化(FSGS)、膜性肾小球肾炎(MGN)、膜增生性肾小球肾炎(MPGN)和新月体肾炎各10例。MCD、FSGS和MGN患者分为非增殖性肾小球肾炎(NPGN)和增殖性肾小球肾炎(PGN)。用Western blotting、免疫荧光和免疫组织化学方法检测肾活检组织中葡萄糖调节蛋白(GRP-78)、生长停滞和DNA损伤诱导蛋白(GADD-153)和Bcl2蛋白的表达。GN(除MCD外)GAdd-153、GRP-78表达上调,且在PGN较NPGN表达更明显(P<0.05),而Bcl2蛋白表达下调(P<0.05)。我们的结果提示,PGD的肾脏损伤与内质网应激有关,内质网应激可能参与了PGN向肾功能衰竭的快速发展。
The role of endoplasmic reticulum (ER) stress in kidney diseases is not well elucidated. Fifty patients with primary glomerular diseases (PGD): minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), and crescentic glomerulonephritis, n = 10 (each group) were enrolled. MCD, FSGS, and MGN patients were sub-grouped as nonproliferative glomerulonephritis (NPGN) and MPGN, RPGN as proliferative glomerulonephritis (PGN). Glucose regulated proteins (GRP-78), growth arrest and DNA damage inducible proteins (GADD-153), and Bcl-2 protein expression was analyzed by Western blotting, immunofluorescence and immunohistochemistry in the kidney biopsy. Up regulation of GADD-153, GRP-78, with more pronounced expression in PGN vs. NPGN (P < 0.05) and down regulation of Bcl-2 proteins was observed in the GN (PGD excluding MCD) as compared to MCD (P < 0.05). Our results suggest that renal injury in PGD is associated with ER stress and ER stress may be involved in the rapid progression of PGN to renal failure.