Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy
Abstract Objectives Among all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic...
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BMC
2024-12-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-024-01546-y |
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| author | Zhibo Hu Yu Zhou Cailing Gao Junfen Liu Congqing Pan Jun Guo |
| author_facet | Zhibo Hu Yu Zhou Cailing Gao Junfen Liu Congqing Pan Jun Guo |
| author_sort | Zhibo Hu |
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| description | Abstract Objectives Among all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic environment is the lysis of renal resident cells. Method This investigation sought to determine whether Astragaloside IV (AS-IV)'s anti-pyroptosis action provides a protective function for the kidneys. For 12 weeks, db/db mice received 40 mg/kg of AS-IV by transgastric gavage. To validate the possible in vitro mechanism, mouse podocytes were cultivated for additional experiments. Results In vitro, AS-IV led to a significant reduction in blood urea nitrogen (BUN), urine albumen-to-creatinine ratio (UACR), serum creatinine (CREA), and hyperglycemia in db/db mice and lessen the pathological alterations in the kidney. Moreover, pyrin structural domain of the NLR family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, gasdermin D (GSDMD), IL-18, and IL-1β were down-expressed and podocyte markers podocin and nphs1 were up-regulated following AS-IV intervention. By silencing GSDMD, we demonstrated in vitro that HG-stimulated podocytes undergo pyroptosis. We also discovered that AS-IV can mitigate this pyroptosis. To confirm that AS-IV prevented the NLRP3 inflammasome from activating, the NLRP3 inhibitor CY-09 was employed. It was also discovered that AS-IV prevents the expression of TXNIP and NLRP3 as well as their interaction. GSDMD expression was significantly downregulated following TXNIP-siRNA treatment, whereas GSDMD expression was upregulated in TXNIP overexpression cells; this upregulation could be undone with AS-IV. Conclusions The anti-pyroptosis effect of AS-IV via the TXNIP-NLRP3-GSDMD axis improves the renal function and podocyte damage of db/db mice and delays the onset of DKD, according to in vivo and in vitro experimental data. |
| format | Article |
| id | doaj-art-ea8dc2cff7e1407bac959303c5972d43 |
| institution | OA Journals |
| issn | 1758-5996 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-ea8dc2cff7e1407bac959303c5972d432025-08-20T02:31:41ZengBMCDiabetology & Metabolic Syndrome1758-59962024-12-0116111610.1186/s13098-024-01546-yAstragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathyZhibo Hu0Yu Zhou1Cailing Gao2Junfen Liu3Congqing Pan4Jun Guo5NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical UniversityAbstract Objectives Among all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic environment is the lysis of renal resident cells. Method This investigation sought to determine whether Astragaloside IV (AS-IV)'s anti-pyroptosis action provides a protective function for the kidneys. For 12 weeks, db/db mice received 40 mg/kg of AS-IV by transgastric gavage. To validate the possible in vitro mechanism, mouse podocytes were cultivated for additional experiments. Results In vitro, AS-IV led to a significant reduction in blood urea nitrogen (BUN), urine albumen-to-creatinine ratio (UACR), serum creatinine (CREA), and hyperglycemia in db/db mice and lessen the pathological alterations in the kidney. Moreover, pyrin structural domain of the NLR family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, gasdermin D (GSDMD), IL-18, and IL-1β were down-expressed and podocyte markers podocin and nphs1 were up-regulated following AS-IV intervention. By silencing GSDMD, we demonstrated in vitro that HG-stimulated podocytes undergo pyroptosis. We also discovered that AS-IV can mitigate this pyroptosis. To confirm that AS-IV prevented the NLRP3 inflammasome from activating, the NLRP3 inhibitor CY-09 was employed. It was also discovered that AS-IV prevents the expression of TXNIP and NLRP3 as well as their interaction. GSDMD expression was significantly downregulated following TXNIP-siRNA treatment, whereas GSDMD expression was upregulated in TXNIP overexpression cells; this upregulation could be undone with AS-IV. Conclusions The anti-pyroptosis effect of AS-IV via the TXNIP-NLRP3-GSDMD axis improves the renal function and podocyte damage of db/db mice and delays the onset of DKD, according to in vivo and in vitro experimental data.https://doi.org/10.1186/s13098-024-01546-yAstragaloside IVDiabetic kidney diseasePyroptosisTXNIPNLRP3 inflammasome |
| spellingShingle | Zhibo Hu Yu Zhou Cailing Gao Junfen Liu Congqing Pan Jun Guo Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy Diabetology & Metabolic Syndrome Astragaloside IV Diabetic kidney disease Pyroptosis TXNIP NLRP3 inflammasome |
| title | Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy |
| title_full | Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy |
| title_fullStr | Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy |
| title_full_unstemmed | Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy |
| title_short | Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy |
| title_sort | astragaloside iv attenuates podocyte apoptosis via regulating txnip nlrp3 gsdmd signaling pathway in diabetic nephropathy |
| topic | Astragaloside IV Diabetic kidney disease Pyroptosis TXNIP NLRP3 inflammasome |
| url | https://doi.org/10.1186/s13098-024-01546-y |
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