TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway
Abstract Atherosclerosis, a critical vascular complication frequently associated with diabetes mellitus, develops due to the synergistic effects of multiple pathological mechanisms. Toll-like receptor-2 (TLR2) has been identified as a key contributor to the progression of a wide range of disorders....
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Nature Portfolio
2025-05-01
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| author | Sisi Chen Min Xie Yong Liu |
| author_facet | Sisi Chen Min Xie Yong Liu |
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| description | Abstract Atherosclerosis, a critical vascular complication frequently associated with diabetes mellitus, develops due to the synergistic effects of multiple pathological mechanisms. Toll-like receptor-2 (TLR2) has been identified as a key contributor to the progression of a wide range of disorders. The primary goal of this research was to investigate the functional role of TLR2 in the context of diabetes mellitus-associated atherosclerosis (DMA) and to delineate the molecular pathways underlying its effects. The study enrolled 30 DMA patients and 30 healthy individuals. An in vitro model of DMA was developed to mimic the disease state. TLR2 expression levels were measured using RT-qPCR, while pyroptosis rates were assessed via flow cytometry. Western blot analysis was utilized to determine protein expression levels. Co-immunoprecipitation was performed to assess the interactions between TLR2 and myeloid differentiation primary response 88 (MyD88). A DMA mouse model was established. Oil red O staining were used to assess the effect of TLR2 on lipid deposition. Elevated levels of TLR2 were observed in both clinical samples from DMA patients and the experimental DMA cell model. The DMA model exhibited reduced cell viability, increased pyroptosis rates, elevated levels of pyroptosis-related proteins, and higher concentrations of interleukin (IL)-1β and IL-18. These effects were reversed upon TLR2 inhibition. Furthermore, inhibition of TLR2 expression effectively blocked the activation of the MyD88/NF-κB signaling pathway. Conversely, TLR2 overexpression reduced cell viability, enhanced pyroptosis, and activated the MyD88/NF-κB pathway, effects that were counteracted by NF-κB inhibition. In in vivo study, silencing of TLR2 improved inflammation and atherosclerosis in diabetic mice. The results demonstrated that TLR2 drives the progression of DMA through the activation of the NLRP3 inflammasome and the MyD88/NF-κB signaling cascade. These findings suggested that TLR2 could be a promising target for therapeutic interventions aimed at treating DMA. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-dbc909d3d5f246ef88ef62de4024b5b82025-08-20T03:53:12ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00843-4TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathwaySisi Chen0Min Xie1Yong Liu2Department of Endocrinology, Renmin Hospital, Hubei University of MedicineDepartment of Endocrinology, Renmin Hospital, Hubei University of MedicineDepartment of Gastroenterology, Renmin Hospital, Hubei University of MedicineAbstract Atherosclerosis, a critical vascular complication frequently associated with diabetes mellitus, develops due to the synergistic effects of multiple pathological mechanisms. Toll-like receptor-2 (TLR2) has been identified as a key contributor to the progression of a wide range of disorders. The primary goal of this research was to investigate the functional role of TLR2 in the context of diabetes mellitus-associated atherosclerosis (DMA) and to delineate the molecular pathways underlying its effects. The study enrolled 30 DMA patients and 30 healthy individuals. An in vitro model of DMA was developed to mimic the disease state. TLR2 expression levels were measured using RT-qPCR, while pyroptosis rates were assessed via flow cytometry. Western blot analysis was utilized to determine protein expression levels. Co-immunoprecipitation was performed to assess the interactions between TLR2 and myeloid differentiation primary response 88 (MyD88). A DMA mouse model was established. Oil red O staining were used to assess the effect of TLR2 on lipid deposition. Elevated levels of TLR2 were observed in both clinical samples from DMA patients and the experimental DMA cell model. The DMA model exhibited reduced cell viability, increased pyroptosis rates, elevated levels of pyroptosis-related proteins, and higher concentrations of interleukin (IL)-1β and IL-18. These effects were reversed upon TLR2 inhibition. Furthermore, inhibition of TLR2 expression effectively blocked the activation of the MyD88/NF-κB signaling pathway. Conversely, TLR2 overexpression reduced cell viability, enhanced pyroptosis, and activated the MyD88/NF-κB pathway, effects that were counteracted by NF-κB inhibition. In in vivo study, silencing of TLR2 improved inflammation and atherosclerosis in diabetic mice. The results demonstrated that TLR2 drives the progression of DMA through the activation of the NLRP3 inflammasome and the MyD88/NF-κB signaling cascade. These findings suggested that TLR2 could be a promising target for therapeutic interventions aimed at treating DMA.https://doi.org/10.1038/s41598-025-00843-4TLR2Diabetes mellitus with atherosclerosisNLRP3MyD88/NF-κB |
| spellingShingle | Sisi Chen Min Xie Yong Liu TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway Scientific Reports TLR2 Diabetes mellitus with atherosclerosis NLRP3 MyD88/NF-κB |
| title | TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway |
| title_full | TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway |
| title_fullStr | TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway |
| title_full_unstemmed | TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway |
| title_short | TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway |
| title_sort | tlr2 promotes the progression of diabetes mellitus with atherosclerosis via activating nlrp3 inflammasome and myd88 nf κb signaling pathway |
| topic | TLR2 Diabetes mellitus with atherosclerosis NLRP3 MyD88/NF-κB |
| url | https://doi.org/10.1038/s41598-025-00843-4 |
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