• Thomas Trian, Benoit Allard, Annaig Ozier, Elise Maurat, Isabelle Dupin, Matthieu Thumerel, Olga Ousova, Jennifer Gillibert-Duplantier, Valérie Le Morvan, Hugues Begueret, Pierre-Olivier Girodet, Roger Marthan, and Patrick Berger.
• Université Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Bordeaux, France. Electronic address: thomas.trian@u-bordeaux.fr.
• J. Allergy Clin. Immunol. 2016 Jun 1; 137 (6): 1717-1726.e13.

BackgroundIncrease of bronchial smooth muscle (BSM) mass is a crucial feature of asthma remodeling. The mechanisms of such an increased BSM mass are complex but involve enhanced mitochondrial biogenesis, leading to increased proliferation of BSM cells in asthmatic patients. The major tumor suppressor protein p53 is a key cell regulator involved in cell proliferation and has also been implicated in mitochondrial biogenesis. However, the role of p53 in BSM cell proliferation and mitochondrial biogenesis has not been investigated thus far.ObjectiveWe sought to evaluate the role of p53 in proliferation of BSM cells in asthmatic patients and mitochondrial biogenesis.MethodsThe expression of p53 was assessed both in vitro by using flow cytometry and Western blotting and ex vivo by using RT-PCR after laser microdissection. The role of p53 was assessed with small hairpin RNA lentivirus in both asthmatic patients and control subjects with BSM cell proliferation by using 5-bromo-2'-deoxyuridine and cell counting and in the expression of p21, BCL2-associated X protein, mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α).ResultsTwenty-nine patients with moderate-to-severe asthma and 26 control subjects were enrolled in the study. p53 expression was increased in BSM from asthmatic patients both ex vivo and in vitro, with a decreased interaction with mouse double minute 2 homolog (Mdm2) and an increased phosphorylation of serine 20. p53 did not inhibit the transcription of both TFAM and PGC-1α in BSM cells from asthmatic patients. As a consequence, p53 is unable to slow the increased mitochondrial biogenesis and hence the subsequent increased proliferation of BSM cells in asthmatic patients.ConclusionThis study suggests that p53 might act as a new potential therapeutic target against BSM remodeling in asthmatic patients.Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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