Hydrogen sulfide, a gaseous signaling molecule, elongates primary cilia on kidney tubular epithelial cells by activating extracellular signal-regulated kinase.
Hydrogen sulfide, a gaseous signaling molecule, elongates primary cilia on kidney tubular epithelial cells by activating extracellular signal-regulated kinase.
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DOI：
10.4196/kjpp.2021.25.6.593
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发表时间：
2021-11-01
期刊：
影响因子：
--
通讯作者：
Park KM
中科院分区：
文献类型：
--
作者：
Han SJ;Kim JI;Lipschutz JH;Park KM
肾小管上皮细胞上的初级纤毛在维持结构和生理功能方面起着重要作用。新出现的证据表明，初级纤毛的缺乏及其长度与肾脏疾病有关。肾小管上皮细胞中初级纤毛的长度至少部分取决于氧化应激和细胞外信号调节激酶1/2（ERK）的激活。硫化氢（H2S）参与抗氧化系统和ERK信号通路。因此，在这项研究中，我们研究了H2S在初级纤毛伸长和下游途径中的作用。在培养的Madin-Darby犬肾细胞中，在细胞生长至融合单层后4天，初级纤毛的长度逐渐增加。此外，硫化氢产生酶的表达增加伴随着初级纤毛长度。用NaHS（一种外源H2S供体）处理，加速初级纤毛的伸长，而DL-炔丙基甘氨酸（一种胱硫醚γ-裂解酶抑制剂）和羟胺（一种胱硫醚-β-合成酶抑制剂）延迟它们的伸长。NaHS处理增加ERK激活和Sec 10和Arl 13 b蛋白表达，这两者都参与纤毛形成和伸长。用ERK抑制剂U 0126处理，延迟了初级纤毛的伸长，并阻断了NaHS介导的初级纤毛伸长和Sec 10和Arl 13 b上调的作用。最后，我们还发现H2S加速缺血性肾损伤后初级纤毛的伸长。这些结果表明，H2S延长初级纤毛通过ERK激活和随后增加Sec 10和Arl 13 b的表达，表明H2S及其下游目标可能是新的分子靶点调节初级纤毛。
Primary cilia on kidney tubular cells play crucial roles in maintaining structure and physiological function. Emerging evidence indicates that the absence of primary cilia, and their length, are associated with kidney diseases. The length of primary cilia in kidney tubular epithelial cells depends, at least in part, on oxidative stress and extracellular signal-regulated kinase 1/2 (ERK) activation. Hydrogen sulfide (H2S) is involved in antioxidant systems and the ERK signaling pathway. Therefore, in this study, we investigated the role of H2S in primary cilia elongation and the downstream pathway. In cultured Madin-Darby Canine Kidney cells, the length of primary cilia gradually increased up to 4 days after the cells were grown to confluent monolayers. In addition, the expression of H2S-producing enzyme increased concomitantly with primary cilia length. Treatment with NaHS, an exogenous H2S donor, accelerated the elongation of primary cilia whereas DL-propargylglycine (a cystathionine γ-lyase inhibitor) and hydroxylamine (a cystathionine-β-synthase inhibitor) delayed their elongation. NaHS treatment increased ERK activation and Sec10 and Arl13b protein expression, both of which are involved in cilia formation and elongation. Treatment with U0126, an ERK inhibitor, delayed elongation of primary cilia and blocked the effect of NaHS-mediated primary cilia elongation and Sec10 and Arl13b upregulation. Finally, we also found that H2S accelerated primary cilia elongation after ischemic kidney injury. These results indicate that H2S lengthens primary cilia through ERK activation and a consequent increase in Sec10 and Arl13b expression, suggesting that H2S and its downstream targets could be novel molecular targets for regulating primary cilia.
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影响因子：
3.4
作者：
Fan, Hai-Ning;Wang, Hai-Jiu;Deng, Yong
通讯作者：
Deng, Yong
影响因子：
2.4
作者：
Wang, Leanne;Weidenfeld, Raphael;Deane, James A.
通讯作者：
Deane, James A.
硫化氢促进神经干细胞增殖和神经元分化，并保护缺氧引起的海马神经发生减少
影响因子：
3.6
作者：
Liu, Dexiang;Wang, Zhen;Hao, Aijun
通讯作者：
Hao, Aijun
影响因子：
4.8
作者：
Wang, R
通讯作者：
Wang, R
影响因子：
--
作者：
BULGER, RE;SIEGEL, FL;PENDERGRASS, R
通讯作者：
PENDERGRASS, R