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H2S alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by regulating macrophage infiltration via inhibition of NLRP3 signaling.
Experimental Cell Research ( IF 3.7 ) Pub Date : 2019-12-14 , DOI: 10.1016/j.yexcr.2019.111779
Yueyuan Zhou 1 , Xiaoyan Zhu 2 , Xuan Wang 1 , Yi Peng 1 , Jiankui Du 3 , Hongling Yin 4 , Hui Yang 1 , Xin Ni 3 , Weiru Zhang 1
Affiliation  

Renal fibrosis is a key pathological feature in chronic kidney diseases (CKDs). Dysregulation of hydrogen sulfide (H2S) homeostasis is implicated in the pathogenesis of CKDs. Here, C57/BL6 mice were allocated to Sham and unilateral ureteral obstruction (UUO) groups, which were treated with NaHS or NLRP3 inflammasome inhibitor 16673-34-0 for 3-14 days. UUO mice displayed downregulation of H2S production and increased macrophage infiltration in obstructed kidneys. H2S donor NaHS treatment attenuated renal damage and fibrosis and inhibited M1 and M2 macrophage infiltration. NLPR3 inflammasome was activated and levels of phosphorylated nuclear factor κB (NF-κB) p65 subunit, phosphorylated signal transducer and activator of transcription 6 (STAT6) and interleukin (IL)-4 protein were increased in the kidneys after UUO. NLRP3 inhibitor inactivated NF-κB and IL-4/STAT6 signaling, suppressed M1 and M2 macrophage infiltration and attenuated renal damage and fibrosis in UUO mice. NaHS treatment also suppressed NLRP3, NF-κB and IL-4/STAT6 activation in the obstructed kidneys. In conclusion, the therapeutic effects of H2S on UUO-induced renal injury and fibrosis are at least in part by inhibition of M1 and M2 macrophage infiltration. H2S suppresses NLRP3 activation and subsequently inactivates NF-κB and IL-4/STAT6 signaling, which may contribute to the anti-inflammatory and anti-fibrotic effects of H2S.

中文翻译:

H2S通过抑制NLRP3信号传导来调节巨噬细胞浸润,从而缓解对单侧输尿管梗阻的肾脏损伤和纤维化。

肾纤维化是慢性肾脏疾病(CKD)的关键病理特征。硫化氢(H2S)动态平衡的失调与CKDs的发病机制有关。在这里,将C57 / BL6小鼠分为假手术和单侧输尿管梗阻(UUO)组,分别用NaHS或NLRP3炎性体抑制剂16673-34-0治疗3-14天。UUO小鼠在阻塞性肾脏中显示出H2S生成的下调和巨噬细胞浸润的增加。H2S供体NaHS治疗可减轻肾脏损害和纤维化,并抑制M1和M2巨噬细胞浸润。UUO后,肾脏中的NLPR3炎性小体被激活,肾脏中的磷酸化核因子κB(NF-κB)p65亚基,磷酸化信号转导子和转录激活子6(STAT6)和白介素(IL)-4蛋白水平升高。NLRP3抑制剂可灭活UUO小鼠的NF-κB和IL-4 / STAT6信号传导,抑制M1和M2巨噬细胞浸润并减轻肾脏损害和纤维化。NaHS治疗还抑制了阻塞性肾脏中的NLRP3,NF-κB和IL-4 / STAT6活化。总之,H2S对UUO诱导的肾损伤和纤维化的治疗作用至少部分是通过抑制M1和M2巨噬细胞浸润来实现的。H2S抑制NLRP3激活,并随后使NF-κB和IL-4 / STAT6信号失活,这可能有助于H2S的抗炎和抗纤维化作用。H2S对UUO诱导的肾损伤和纤维化的治疗作用至少部分是通过抑制M1和M2巨噬细胞浸润来实现的。H2S抑制NLRP3激活,并随后使NF-κB和IL-4 / STAT6信号失活,这可能有助于H2S的抗炎和抗纤维化作用。H2S对UUO诱导的肾损伤和纤维化的治疗作用至少部分是通过抑制M1和M2巨噬细胞浸润来实现的。H2S抑制NLRP3激活,并随后使NF-κB和IL-4 / STAT6信号失活,这可能有助于H2S的抗炎和抗纤维化作用。
更新日期:2019-12-17
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