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H₂S promotes proliferation of endometrial stromal cells via activating the NF-?B pathway in endometriosis.

ABSTRACT: Hydrogen sulfide (H₂S) is substantially converted from cysteine by the enzymes cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CSE). H₂S can profoundly affect most organ systems in animals and humans by inducing a wide range of physiological functions. However, the roles of H₂S in the progression of endometriosis remain unknown. The aim of the current study was to test the hypothesis that H₂S might play a role in the pathogenesis of endometriosis via modulating the biological behavior of endometrial stromal cells (ESCs). First, we explored the expression level of CBS and CSE in ESCs via immunohistochemistry and immunocytochemistry. Second, cell Count Kit-8 (CCK-8) assays were utilized to investigate the cell viability of human ESCs (HESCs) in vitro. Third, we studied the potential effects of H₂S in a rodent model of endometriosis. Both CBS and CSE were overexpressed in endometriotic lesions. Exogenous and endogenous H₂S could promote HESC proliferation in vitro. Furthermore, this pro-proliferation effect could be reversed by treating with inhibitors of CBS, CSE, or the NF-?B pathway. In vivo, we uncovered that inhibitors of CBS and CSE could remarkably reduce the number and weight of mouse endometriotic lesions. These data suggested that H₂S promotes ESC proliferation via activation of the NF-?B pathway, which provides a scientific basis for the clinical application of blocking H₂S to treat endometriosis.

SUBMITTER: Lei S

PROVIDER: S-EPMC6325523 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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H2S promotes proliferation of endometrial stromal cells via activating the NF-κB pathway in endometriosis.

Lei Shating S Cao Yanling Y Sun Jing J Li Mingqing M Zhao Dong D

American journal of translational research 20181215 12

Hydrogen sulfide (H2S) is substantially converted from cysteine by the enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). H2S can profoundly affect most organ systems in animals and humans by inducing a wide range of physiological functions. However, the roles of H2S in the progression of endometriosis remain unknown. The aim of the current study was to test the hypothesis that H2S might play a role in the pathogenesis of endometri ...[more]

PMID: 30662667

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Project description:BackgroundEndometrial carcinoma (EC) is one of the most common gynecological malignancies among women. Maternal embryonic leucine Zipper Kinase (MELK) is upregulated in a variety of human tumors, where it contributes to malignant phenotype and correlates with a poor prognosis. However, the biological function of MELK in EC progression remains largely unknown.MethodsWe explored the MELK expression in EC using TCGA and GEO databases and verified it using clinical samples by IHC methods. CCK-8 assay, colony formation assay, cell cycle assay, wound healing assay and subcutaneous xenograft mouse model were generated to estimate the functions of MELK and its inhibitor OTSSP167. qRT-PCR, western blotting, co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanism concerning MELK during the progression of EC.FindingsMELK was significantly elevated in patients with EC, and high expression of MELK was associated with serous EC, high histological grade, advanced clinical stage and reduced overall survival and disease-free survival. MELK knockdown decreased the ability of cell proliferation and migration in vitro and subcutaneous tumorigenesis in vivo. In addition, high expression of MELK could be regulated by transcription factor E2F1. Moreover, we found that MELK had a direct interaction with MLST8 and then activated mTORC1 and mTORC2 signaling pathway for EC progression. Furthermore, OTSSP167, an effective inhibitor, could inhibit cell proliferation driven by MELK in vivo and vitro assays.InterpretationWe have explored the crucial role of the E2F1/MELK/mTORC1/2 axis in the progression of EC, which could be served as potential therapeutic targets for treatment of EC.FundingThis research was supported by National Natural Science Foundation of China (No:81672565), the Natural Science Foundation of Shanghai (Grant NO:17ZR1421400 to Dr. Zhihong Ai) and the fundamental research funds for central universities (No: 22120180595).

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H₂S promotes proliferation of endometrial stromal cells via activating the NF-?B pathway in endometriosis.

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H<sub>2</sub>S promotes proliferation of endometrial stromal cells via activating the NF-κB pathway in endometriosis.

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Dataset Information

H2S promotes proliferation of endometrial stromal cells via activating the NF-?B pathway in endometriosis.

Publications

H<sub>2</sub>S promotes proliferation of endometrial stromal cells via activating the NF-κB pathway in endometriosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

H₂S promotes proliferation of endometrial stromal cells via activating the NF-?B pathway in endometriosis.