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| Status |
Public on Aug 15, 2017 |
| Title |
Inhibition of GGPPS1 attenuated LPS-induced acute lung injury by suppressing the NLRP3 inflammasome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: Geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, regulates various pathological processes through balancing the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. We sought to investigate whether GGPPS1 plays a role in mediating acute lung injury (ALI) using a mouse model of inflammation.
Methods: Lipopolysaccharide (LPS) was intra-tracheally instilled to induce ALI in lung specific GGPPS1 knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells (AECs) was examined at different time points. Alveolar exudate, neutrophil infiltration, lung injury and cell death were determined. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro.
Results: GGPPS1 levels increased significantly in lung tissues from LPS-induced ALI mice, where it showed a time- and dose-dependent increase in alveolar epithelial cells. Specific deletion of pulmonary GGPPS1 reduced the alveolar exudate and attenuated the severity of lung injury through inhibiting apoptosis of AECs. However, GGPPS1 deletion had limited effect on neutrophil counts and TNF-α levels in alveolar fluids. Deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1β release and pyroptosis, by down-regulating NLRP3 expression.
Conclusions: Inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI, predominantly by suppressing NLRP3 inflammasome activation.
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| Overall design |
A total of 8 samples from mice treated with LPS in lung specific GGPPS1 knockout and wild-type mice (n=4 for each group)
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| Contributor(s) |
Xu W, Song Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 30, 2016 |
| Last update date |
Feb 02, 2018 |
| Contact name |
wujian xu |
| E-mail(s) |
wujian_xu@163.com
|
| Organization name |
Jinling Hospital
|
| Department |
The department of respiratory disease
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| Street address |
305 Esat Zhongshan Road
|
| City |
Nanjing |
| State/province |
Jiangshu |
| ZIP/Postal code |
210000 |
| Country |
China |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA351748 |
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