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PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in bronchiolar club cells

Karnati, Srikanth ; Oruqaj, Gani ; Janga, Harshavardhan ; Tumpara, Srinu ; Colasante, Claudia ; Van Veldhoven, Paul P. ; Braverman, Nancy ; Pilatz, Adrian ; Mariani, Thomas J. ; Baumgart-Vogt, Eveline


Originalveröffentlichung: (2018) PLOS ONE 13(9):e0203466 doi: 10.1371/journal.pone.0203466
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URN: urn:nbn:de:hebis:26-opus-146259
URL: http://geb.uni-giessen.de/geb/volltexte/2019/14625/

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Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universität Gießen
Institut: Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology
Fachgebiet: Medizin
DDC-Sachgruppe: Medizin
Dokumentart: Aufsatz
Sprache: Englisch
Erstellungsjahr: 2018
Publikationsdatum: 20.05.2019
Kurzfassung auf Englisch: 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.
Lizenz: Lizenz-Logo  Creative Commons - Namensnennung 4.0