Diabetes, obesity & metabolism · 2026
Metformin Alleviates High Glucose-Induced Pyroptosis and Inflammatory Responses in HK-2 Cells via SIRT1-Associated Regulation of the TXNIP/NLRP3 Pathway.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shi Shuyu, Wang Bing, Zhou Yang, Li Qi, Hou Yusheng, Zhang Xinyi, Wang Qiuyue
Аннотация
BACKGROUND: Diabetic kidney disease (DKD) is a major cause of renal failure and end-stage renal disease. Pyroptosis, a Gasdermin-dependent inflammatory form of programmed cell death, has been implicated in DKD progression. Metformin has shown renoprotective effects in DKD; however, the underlying mechanisms remain unclear.
OBJECTIVE: To investigate whether metformin attenuates high glucose-induced pyroptosis and inflammatory responses in HK-2 cells through SIRT1-mediated regulation of the TXNIP/NLRP3 pathway.
METHODS: Bioinformatics analyses were performed to identify DKD-related pyroptosis-associated genes and enriched pathways. Serum TXNIP and IL-1β levels were measured in patients with type 2 diabetes mellitus stratified by urinary albumin-to-creatinine ratio (UACR). HK-2 cells were exposed to high glucose (30 mM) to establish an in vitro injury model. Oxidative stress, pyroptosis-related signalling and inflammatory cytokines were evaluated using molecular and immunological assays. SIRT1 modulation and TXNIP silencing were used to investigate pathway regulation. Chromatin immunoprecipitation assays were performed to assess SIRT1 occupancy and histone acetylation status within the TXNIP promoter region.
RESULTS: Pyroptosis-related genes were mainly enriched in inflammatory and NLRP3 inflammasome-associated pathways. Serum TXNIP and IL-1β levels were elevated in DKD patients and positively correlated with UACR. In HK-2 cells, high glucose reduced SIRT1 expression and activated the TXNIP/NLRP3 inflammasome pathway, accompanied by increased GSDMD cleavage and inflammatory cytokine expression. Metformin partially reversed these changes. Altered SIRT1 activity was also associated with changes in H3K56 acetylation enrichment within the TXNIP promoter region.
CONCLUSION: Metformin may alleviate high glucose-induced pyroptosis and inflammatory responses in HK-2 cells, potentially through modulation of SIRT1-associated TXNIP/NLRP3 signalling and TXNIP-related chromatin acetylation status.
OBJECTIVE: To investigate whether metformin attenuates high glucose-induced pyroptosis and inflammatory responses in HK-2 cells through SIRT1-mediated regulation of the TXNIP/NLRP3 pathway.
METHODS: Bioinformatics analyses were performed to identify DKD-related pyroptosis-associated genes and enriched pathways. Serum TXNIP and IL-1β levels were measured in patients with type 2 diabetes mellitus stratified by urinary albumin-to-creatinine ratio (UACR). HK-2 cells were exposed to high glucose (30 mM) to establish an in vitro injury model. Oxidative stress, pyroptosis-related signalling and inflammatory cytokines were evaluated using molecular and immunological assays. SIRT1 modulation and TXNIP silencing were used to investigate pathway regulation. Chromatin immunoprecipitation assays were performed to assess SIRT1 occupancy and histone acetylation status within the TXNIP promoter region.
RESULTS: Pyroptosis-related genes were mainly enriched in inflammatory and NLRP3 inflammasome-associated pathways. Serum TXNIP and IL-1β levels were elevated in DKD patients and positively correlated with UACR. In HK-2 cells, high glucose reduced SIRT1 expression and activated the TXNIP/NLRP3 inflammasome pathway, accompanied by increased GSDMD cleavage and inflammatory cytokine expression. Metformin partially reversed these changes. Altered SIRT1 activity was also associated with changes in H3K56 acetylation enrichment within the TXNIP promoter region.
CONCLUSION: Metformin may alleviate high glucose-induced pyroptosis and inflammatory responses in HK-2 cells, potentially through modulation of SIRT1-associated TXNIP/NLRP3 signalling and TXNIP-related chromatin acetylation status.