Jung Kyong-Jin, Jang Hee-Seong, Kim Jee In, Han Sang Jun, Park Jeen-Woo, Park Kwon Moo
Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Biochim Biophys Acta. 2013 Dec;1832(12):1989-97. doi: 10.1016/j.bbadis.2013.06.015. Epub 2013 Jul 9.
Hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in the transsulfuration pathway of homocysteine plays a number of pathophysiological roles. Hyperhomocysteinemia is involved in kidney fibrosis. However, the role of H2S in kidney fibrosis remains to be defined. Here, we investigated the role of H2S and its acting mechanism in unilateral ureteral obstruction (UO)-induced kidney fibrosis in mice. UO decreased expressions of CBS and CSE in the kidney with decrease of H2S concentration. Treatment with sodium hydrogen sulfide (NaHS, a H2S producer) during UO reduced UO-induced oxidative stress with preservations of catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) expression, and glutathione level. In addition, NaHS mitigated decreases of CBS and CSE expressions, and H2S concentration in the kidney. NaHS treatment attenuated UO-induced increases in levels of TGF-β1, activated Smad3, and activated NF-κB. This study provided the first evidence of involvement of the transsulfuration pathway and H2S in UO-induced kidney fibrosis, suggesting that H2S and its transsulfuration pathway may be a potential target for development of therapeutics for fibrosis-related diseases.
同型半胱氨酸转硫途径中的胱硫醚β-合酶（CBS）和胱硫醚γ-裂解酶（CSE）产生的硫化氢（H2S）发挥着多种病理生理作用。高同型半胱氨酸血症与肾纤维化有关。然而，H2S在肾纤维化中的作用仍有待确定。在此，我们研究了H2S在小鼠单侧输尿管梗阻（UO）诱导的肾纤维化中的作用及其作用机制。UO导致肾脏中CBS和CSE的表达降低，同时H2S浓度下降。在UO期间用硫化氢钠（NaHS，一种H2S生成剂）治疗可减轻UO诱导的氧化应激，同时保留过氧化氢酶、铜锌超氧化物歧化酶（CuZnSOD）和锰超氧化物歧化酶（MnSOD）的表达以及谷胱甘肽水平。此外，NaHS减轻了肾脏中CBS和CSE表达以及H2S浓度的下降。NaHS治疗减弱了UO诱导的TGF-β1、活化的Smad3和活化的NF-κB水平的升高。本研究首次提供了转硫途径和H2S参与UO诱导的肾纤维化的证据，表明H2S及其转硫途径可能是开发纤维化相关疾病治疗药物的潜在靶点。
