pNaKtide ameliorates renal interstitial fibrosis through inhibition of sodium-potassium adenosine triphosphatase-mediated signaling pathways in unilateral ureteral obstruction mice
pNaKtide ameliorates renal interstitial fibrosis through inhibition of sodium-potassium adenosine triphosphatase-mediated signaling pathways in unilateral ureteral obstruction mice
复制标题
pNaKtide 通过抑制单侧输尿管梗阻小鼠中钠钾腺苷三磷酸酶介导的信号通路改善肾间质纤维化
DOI：
10.1093/ndt/gfy107
复制
发表时间：
2019-02-01
影响因子：
6.1
通讯作者：
Wang, Yu
中科院分区：
文献类型：
--
作者：
Cheng, Xi;Song, Yi;Wang, Yu
背景
Background
Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO.
Methods
UUO was performed on male C57BL/6J mice. pNaKtide, a mimic of Na/K-ATPase, was administered by intraperitoneal injection on Day 0 and Day 4 after ureteral ligation. Markers of interstitial fibrosis, inflammation and oxidative stress and transforming growth factor-β1 (TGF-β1) expression were examined after the mice were sacrificed on Day 7. Activation of Src and its downstream signaling effectors, including extracellular regulated protein kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase B (AKT), were evaluated.
Results
pNaKtide administration markedly attenuated myofibroblast accumulation and extracellular matrix deposition in obstructed kidneys. Also, pNaKtide significantly reduced the increased expression of 8-iso-prostaglandin F2α, TGF-β1, interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), as well as reduced macrophage infiltration, in UUO animals. All these changes were obtained, along with inhibition of Src and its downstream effector activity.
Conclusions
Na/K-ATPase-mediated signaling pathways contribute to fibrogenesis and could represent a potential target in the treatment of renal fibrosis.