ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis
ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis
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DOI：
10.1152/ajprenal.00124.2009
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Kagami, Shoji
中科院分区：
文献类型：
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作者：
Urushihara, Maki;Takamatsu, Masanori;Kagami, Shoji
Urushihara M, Takamatsu M, Shimizu M, Kondo S, Kinoshita Y, Suga K, Kitamura A, Matsuura S, Yoshizumi M, Tamaki T, Kawachi H, Kagami S. ERK5激活提高大鼠进行性肾小球肾炎系膜细胞活力和胶原基质积累。[J]中国生物医学工程学报，2016,32(5):557 - 557。首次发表于2009年10月21日；doi: 10.1152 / ajprenal.00124.2009。丝裂原活化蛋白激酶（MAPK）级联在肾小球肾炎（GN）的多种细胞功能调控中起重要作用。在这里，我们研究了细胞外信号调节激酶5 (ERK5)， MAPK家族的一员，是否参与慢性血管增生性GN的发病机制，使用非肾切除和注射抗y-1抗体诱导的大鼠模型。在不同时间点获得的肾脏免疫染色显示，phospho-ERK5在对照肾小球中表达较弱，但在GN 28和56天后，在典型的肾小球系膜模式中表达显著增加。半定量评估表明，肾小球磷酸化erk5的表达与细胞外基质（ECM）、I型胶原的积累以及肾小球活性氧（ROS）和ANG II的表达密切相关。另一方面，phospho-ERK1/2的表达在系膜细胞（MC）增殖增强期的第7天升高，随后下降。H(2)O(2)和ANG II分别诱导培养的大鼠MCs磷酸化ERK5。H(2)O(2)和ANG II的共刺激可协同增加MCs中ERK5的磷酸化。转染erk5特异性小干扰RNA的培养MCs与对照细胞相比，H(2)O(2)或ANG ii诱导的细胞活力和可溶性胶原分泌显著降低。用ANG II型1受体阻滞剂治疗GN大鼠，导致磷酸化- erk5表达和胶原积累显著降低，并伴有明显的组织学改善。综上所述，这些结果表明，在慢性GN实验模型中，ANG II或H(2)O(2)磷酸化MC ERK5可增强细胞活力和ECM积累。
Urushihara M, Takamatsu M, Shimizu M, Kondo S, Kinoshita Y, Suga K, Kitamura A, Matsuura S, Yoshizumi M, Tamaki T, Kawachi H, Kagami S. ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. Am J Physiol Renal Physiol 298: F167-F176, 2010. First published October 21, 2009; doi:10.1152/ajprenal.00124.2009.-The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN.