Karnati, SrikanthSrikanthKarnatiOruqaj, GaniGaniOruqajJanga, HarshavardhanHarshavardhanJangaTumpara, SrinuSrinuTumparaColasante, ClaudiaClaudiaColasanteVan Veldhoven, Paul P.Paul P.Van VeldhovenBraverman, NancyNancyBravermanPilatz, AdrianAdrianPilatzMariani, Thomas J.Thomas J.MarianiBaumgart-Vogt, EvelineEvelineBaumgart-Vogt2022-11-182019-05-202022-11-182018http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146259https://jlupub.ub.uni-giessen.de/handle/jlupub/9460http://dx.doi.org/10.22029/jlupub-8848Despite 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.enNamensnennung 4.0 Internationalddc:610