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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Wang, Diya Wang, Minghao Sun, Shukai Zhang, Chongyang Song, Ya Li, Jianing Song, Bing Lv, Haipeng Wang, Shengchao Jiang, Wenkai |
| Abstract | Background Previous studies have reported the link between hypoxic conditions and NLRP3 inflammasome-mediated pulpal inflammation in the progression of pulpitis. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the role of HIF-1α in the regulation of NLRP3 inflammasome pathway via NF-κB signaling under hypoxic conditions with or without LPS in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. Methods HIF-1α plasmids or siRNAs were used to upregulate or downregulate HIF-1α in HDPFs, respectively. The effect of hypoxia with or without LPS on the NF-κB signaling and NLRP3 inflammasome pathway was analyzed by immunofluorescence staining, qRT-PCR, western blotting and ELISA. Results The hypoxic conditions alone induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling in a time-dependent manner in HDPFs. The upregulation of HIF-1α further promoted hypoxia-induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. In comparison, downregulation of HIF-1α inhibited ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Additionally, LPS plus hypoxia further promoted HIF-1α expression and NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Conclusions HIF-1α served as a positive regulator of NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling in HDPFs in the sterile pulpal inflammation and caries-related pulpitis microenvironment. The finding of a novel functional HIF-1α-NF-κB-NLRP3 axis provides insight into the link between the hypoxic microenvironment and pulpal inflammation, thus supporting a promising therapeutic strategy for the control of pulpal inflammation. |
| Related Links | https://bmcoralhealth.biomedcentral.com/counter/pdf/10.1186/s12903-024-04936-w.pdf |
| Ending Page | 10 |
| Page Count | 10 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14726831 |
| DOI | 10.1186/s12903-024-04936-w |
| Journal | BMC Oral Health |
| Issue Number | 1 |
| Volume Number | 24 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-09-29 |
| Access Restriction | Open |
| Subject Keyword | Dentistry Oral and Maxillofacial Surgery NLRP3 HIF-1α Human dental pulp fibroblasts Pulpitis Sterile inflammation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Dentistry |
| Journal Impact Factor | 2.6/2023 |
| 5-Year Journal Impact Factor | 3.2/2023 |
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