PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in bronchiolar club cells
dc.contributor.author | Karnati, Srikanth | |
dc.contributor.author | Oruqaj, Gani | |
dc.contributor.author | Janga, Harshavardhan | |
dc.contributor.author | Tumpara, Srinu | |
dc.contributor.author | Colasante, Claudia | |
dc.contributor.author | Van Veldhoven, Paul P. | |
dc.contributor.author | Braverman, Nancy | |
dc.contributor.author | Pilatz, Adrian | |
dc.contributor.author | Mariani, Thomas J. | |
dc.contributor.author | Baumgart-Vogt, Eveline | |
dc.date.accessioned | 2022-11-18T09:53:45Z | |
dc.date.available | 2019-05-20T13:34:26Z | |
dc.date.available | 2022-11-18T09:53:45Z | |
dc.date.issued | 2018 | |
dc.description.abstract | Despite the important functions of PPARgamma in various cell types of the lung, PPARgamma-deficiency in club cells induces only mild emphysema. Peroxisomes are distributed in a similar way as PPARγ in the lung and are mainly enriched in club and AECII cells. To date, the effects of PPARgamma-deficiency on the overall peroxisomal compartment and its metabolic alterations in pulmonary club cells are unknown. Therefore, we characterized wild-type and club cell-specific PPARgamma knockout-mice lungs and used C22 cells to investigate the peroxisomal compartment and its metabolic roles in the distal airway epithelium by means of 1) double-immunofluorescence labelling for peroxisomal proteins, 2) laser-assisted microdissection of the bronchiolar epithelium and subsequent qRT-PCR, 3) siRNA-transfection of PPARgamma and PPRE dual-luciferase reporter activity in C22 cells, 4) PPARg inhibition by GW9662, 5) GC-MS based lipid analysis. Our results reveal elevated levels of fatty acids, increased expression of PPARalpha and PPRE activity, a strong overall upregulation of the peroxisomal compartment and its associated gene expression (biogenesis, alpha-oxidation, beta-oxidation, and plasmalogens) in PPARgamma-deficient club cells. Interestingly, catalase was significantly increased and mistargeted into the cytoplasm, suggestive for oxidative stress by the PPARgamma-deficiency in club cells. Taken together, PPARalpha-mediated metabolic induction and proliferation of peroxisomes via a PPRE-dependent mechanism could compensate PPARgamma-deficiency in club cells. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146259 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9460 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-8848 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.ddc | ddc:610 | de_DE |
dc.title | PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in bronchiolar club cells | en |
dc.type | article | de_DE |
local.affiliation | FB 11 - Medizin | de_DE |
local.opus.fachgebiet | Medizin | de_DE |
local.opus.id | 14625 | |
local.opus.institute | Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology | de_DE |
local.source.freetext | PLOS ONE 13(9):e0203466 | de_DE |
local.source.uri | https://doi.org/10.1371/journal.pone.0203466 |
Dateien
Originalbündel
1 - 1 von 1
Lade...
- Name:
- 10.1371_journal.pone.0203466.pdf
- Größe:
- 11.4 MB
- Format:
- Adobe Portable Document Format