Wang Xuan, Lin Tao, He Yifei, Zhou Yueyuan, Peng Yi, Zhang Weiru, Ni Xin
Department of General Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
International Collaborative Research Center for Medical Metabolomics, Xiangya Hospital, Central South University, Changsha 410008, China.
Biology (Basel). 2023 Feb 16;12(2):318. doi: 10.3390/biology12020318.
The molecular mechanisms underlying lupus nephritis (LN) pathogenesis are not fully understood. Hydrogen sulfide (H2S) is involved in many pathological and physiological processes. We sought to investigate the roles of H2S in LN pathogenesis. H2S synthase cystathionine-lyase (CSE) and cystathionine-synthetase (CBS) expression was downregulated in renal tissues of patients with LN and their levels were associated with LN's prognosis using the Nephroseq database. Reduced CSE and CBS protein expression in kidney tissues of LN patients and MRL/lpr mice were confirmed by immunohistochemistry. CSE and CBS mRNA levels were reduced in MRL/lpr and pristine- and R848-induced lupus mice. Given that H2S exerts an anti-inflammatory role partly via regulating inflammatory transcription factors (TFs), we analyzed hub TFs by using a bioinformatics approach. It showed that STAT1, RELA, and T-cell-related signaling pathways were enriched in LN. Increased STAT1 and RELA expression were confirmed in renal tissues of LN patients. Treatment of MRL/lpr and pristine mice with H2S donors alleviated systemic lupus erythematosus (SLE) phenotypes and renal injury. H2S donors inhibited RELA level and T-cell infiltration in the kidneys of MRL/lpr and pristine mice. Our data indicated that CSE/CBS/H2S contributes to LN pathogenesis. Supplementation of H2S would be a potential therapeutic strategy for LN.
狼疮性肾炎（LN）发病机制的分子机制尚未完全阐明。硫化氢（H2S）参与许多病理和生理过程。我们试图研究H2S在LN发病机制中的作用。利用Nephroseq数据库发现，H2S合酶胱硫醚裂解酶（CSE）和胱硫醚合成酶（CBS）在LN患者肾组织中的表达下调，其水平与LN的预后相关。免疫组化证实LN患者及MRL/lpr小鼠肾组织中CSE和CBS蛋白表达降低。在MRL/lpr以及未处理和R848诱导的狼疮小鼠中，CSE和CBS mRNA水平降低。鉴于H2S部分通过调节炎症转录因子（TFs）发挥抗炎作用，我们采用生物信息学方法分析了关键TFs。结果显示，STAT1、RELA和T细胞相关信号通路在LN中富集。在LN患者肾组织中证实STAT1和RELA表达增加。用H2S供体治疗MRL/lpr和未处理小鼠可减轻系统性红斑狼疮（SLE）表型和肾损伤。H2S供体抑制MRL/lpr和未处理小鼠肾脏中RELA水平和T细胞浸润。我们的数据表明，CSE/CBS/H2S参与LN发病机制。补充H2S可能是LN的一种潜在治疗策略。
