دورية أكاديمية
PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in bronchiolar club cells
| العنوان: | PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in bronchiolar club cells |
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| المؤلفون: | Karnati, Srikanth, Oruqaj, Gani, Janga, Harshavardhan, Tumpara, Srinu, Colasante, Claudia, Van Veldhoven, Paul P., Braverman, Nancy, Pilatz, Adrian, Mariani, Thomas J., Baumgart-Vogt, Eveline |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | ddc:610 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146259Test; https://jlupub.ub.uni-giessen.de//handle/jlupub/9460Test; http://dx.doi.org/10.22029/jlupub-8848Test |
| DOI: | 10.22029/jlupub-8848 |
| الإتاحة: | https://doi.org/10.22029/jlupub-8848Test https://jlupub.ub.uni-giessen.de//handle/jlupub/9460Test http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146259Test |
| حقوق: | Namensnennung 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.843E100F |
| قاعدة البيانات: | BASE |
| DOI: | 10.22029/jlupub-8848 |
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