Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway
The body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial ro...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/7/927 |
| _version_ | 1797407297291419648 |
|---|---|
| author | Yuanyuan Liu Nianyu Xue Boxi Zhang Hongming Lv Shize Li |
| author_facet | Yuanyuan Liu Nianyu Xue Boxi Zhang Hongming Lv Shize Li |
| author_sort | Yuanyuan Liu |
| collection | DOAJ |
| description | The body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial role in liver diseases. However, the role of pyroptosis in cold stress-induced liver injury is not clear. Hence, in this study, we attempted to investigate the effects of chronic cold exposure on liver function, apoptosis, oxidative stress and inflammation in mice by establishing a mouse model of chronic cold exposure, and to investigate whether pyroptosis pathways are involved in the process of chronic cold exposure. In vivo, our results show that inflammatory cell infiltration and other pathological changes in liver cells and the activity of liver enzyme evidently increased in the serum and liver of cold-exposed mice, suggesting cold stress may result in liver injury. Remarkably, increased expression of heat shock protein 70 (HSP70) and HSP90 proteins proved the cold stress model is successfully constructed. Then, elevated levels of apoptosis, inflammation, oxidative stress and pyroptosis related proteins and mRNAs, such as cysteinyl aspartate specific proteinase-3 (Caspase-3), inducible nitric oxide synthase (iNOS), nuclear factor erythroid2-related factor 2 (Nrf2) and gasdermins D (GSDMD), confirmed that cold exposure activated apoptosis, oxidative stress and pyroptosis, and released inflammation cytokines. Meanwhile, in vitro, we got similar results as in vivo. Further, adding an NLR family pyrin domain containing 3 (NLRP3) inhibitors found that suppression expression of NLRP3 results in the essential proteins of pyroptosis and antioxidant evidently reduced, and adding GSDMD inhibitor found that suppression expression of GSDMD accompanies with the level of Nrf2 and heme oxygenase-1 (HO-1) obviously reduced. In summary, these findings provide a new understanding of the underlying mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia. |
| first_indexed | 2024-03-09T03:39:18Z |
| format | Article |
| id | doaj.art-4efadcc1947d493ca8fdbc092adc91c6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T03:39:18Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4efadcc1947d493ca8fdbc092adc91c62023-12-03T14:43:25ZengMDPI AGBiomolecules2218-273X2022-07-0112792710.3390/biom12070927Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling PathwayYuanyuan Liu0Nianyu Xue1Boxi Zhang2Hongming Lv3Shize Li4National Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, ChinaNational Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, ChinaNational Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, ChinaNational Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, ChinaNational Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, ChinaThe body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial role in liver diseases. However, the role of pyroptosis in cold stress-induced liver injury is not clear. Hence, in this study, we attempted to investigate the effects of chronic cold exposure on liver function, apoptosis, oxidative stress and inflammation in mice by establishing a mouse model of chronic cold exposure, and to investigate whether pyroptosis pathways are involved in the process of chronic cold exposure. In vivo, our results show that inflammatory cell infiltration and other pathological changes in liver cells and the activity of liver enzyme evidently increased in the serum and liver of cold-exposed mice, suggesting cold stress may result in liver injury. Remarkably, increased expression of heat shock protein 70 (HSP70) and HSP90 proteins proved the cold stress model is successfully constructed. Then, elevated levels of apoptosis, inflammation, oxidative stress and pyroptosis related proteins and mRNAs, such as cysteinyl aspartate specific proteinase-3 (Caspase-3), inducible nitric oxide synthase (iNOS), nuclear factor erythroid2-related factor 2 (Nrf2) and gasdermins D (GSDMD), confirmed that cold exposure activated apoptosis, oxidative stress and pyroptosis, and released inflammation cytokines. Meanwhile, in vitro, we got similar results as in vivo. Further, adding an NLR family pyrin domain containing 3 (NLRP3) inhibitors found that suppression expression of NLRP3 results in the essential proteins of pyroptosis and antioxidant evidently reduced, and adding GSDMD inhibitor found that suppression expression of GSDMD accompanies with the level of Nrf2 and heme oxygenase-1 (HO-1) obviously reduced. In summary, these findings provide a new understanding of the underlying mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.https://www.mdpi.com/2218-273X/12/7/927cold stresspyroptosisinflammasomeapoptosisliver injury |
| spellingShingle | Yuanyuan Liu Nianyu Xue Boxi Zhang Hongming Lv Shize Li Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway Biomolecules cold stress pyroptosis inflammasome apoptosis liver injury |
| title | Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway |
| title_full | Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway |
| title_fullStr | Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway |
| title_full_unstemmed | Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway |
| title_short | Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway |
| title_sort | cold stress induced liver injury of mice through activated nlrp3 caspase 1 gsdmd pyroptosis signaling pathway |
| topic | cold stress pyroptosis inflammasome apoptosis liver injury |
| url | https://www.mdpi.com/2218-273X/12/7/927 |
| work_keys_str_mv | AT yuanyuanliu coldstressinducedliverinjuryofmicethroughactivatednlrp3caspase1gsdmdpyroptosissignalingpathway AT nianyuxue coldstressinducedliverinjuryofmicethroughactivatednlrp3caspase1gsdmdpyroptosissignalingpathway AT boxizhang coldstressinducedliverinjuryofmicethroughactivatednlrp3caspase1gsdmdpyroptosissignalingpathway AT hongminglv coldstressinducedliverinjuryofmicethroughactivatednlrp3caspase1gsdmdpyroptosissignalingpathway AT shizeli coldstressinducedliverinjuryofmicethroughactivatednlrp3caspase1gsdmdpyroptosissignalingpathway |