Methionine Restriction Prevents Lipopolysaccharide-Induced Acute Lung Injury via Modulating CSE/H2S Pathway.
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ABSTRACT:
SUBMITTER: Duan J
PROVIDER: S-EPMC8777780 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:Purpose: Hepatic stellate cell (HSC) and Hydrogen sulfide (H2S) both play important roles in Hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participates in regulating the biological process of HCC cells by releasing H2S remains elusive. In this study, we investigate how activated HSC influence HCC fate. Methods: The effects of LX-2 and H2S on biological functions of HCC cells were analyzed with Flow cytometry and CCK-8. RNA-sequencing, Western blotting, Quantitative real-time reverse transcription PCR (RT-qPCR), siRNA, immunofluorescence and chromatin immunoprecipitation (ChIP) assays were carried out to examine the effect of H2S on JNK/JunB-TNFSF14 (tumor necrosis factor superfamily member 14) signaling pathway. Specimens from HCC patients were analyzed by using RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Results: LX-2 cells is able to induce HepG2 and PLC/PRF/5 cells apoptosis by releasing H2S. RNA- sequencing results showed that TNFSF14 gene was changed in both LX-2 and NaHS group. NaHS dosage and time-dependently up-regulated TNFSF14 mRNA and protein expression in both HepG2 and PLC/PRF/5 cells. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, mRNA and protein expressions of TNFSF14 in HCC tissues was lower than in the adjacent tissue. HCC patients with low expression of TNFSF14 have higher malignant degree and poor prognosis. Conclusions: Demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.
2022-03-22 | GSE193660 | GEO
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