Lack of Dystrophin Affects Bronchial Epithelium in mdx Mice

Abstract

Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc.

Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice

“…However, the levels of Cx39 protein, a marker associated with active regeneration in damaged muscle (Frinchi et al, ), were not significantly different in the diaphragm of mdx ‐EX and mdx ‐SD mice. The diaphragm, but not limb muscles, of mdx ‐EX and mdx ‐SD mice showed decreased Hsp60 expression at 45 days, suggesting exhaustion of potentially protective mechanisms in the diaphragm, similar to our previous findings in lung epithelium (Morici et al, ). No change in Hsp70 or in the p65 subunit of NF‐kB were detected in the mdx diaphragm, irrespective of training, at variance with the changes observed in limb muscles.…”

“…In wild‐type mice, Hsp60 increased in soleus muscles after 45 days of training (Barone et al, ). In airway epithelium of mdx mice, Hsp60 expression initially increased (30 days), then decreased (45 days) irrespective of training; the fall in Hsp60 expression at 45 days was associated with increased apoptosis of epithelial cells, suggesting a protective role of Hsp60 in the lung (Morici et al, ). As the time course of Hsp60 in diaphragm and skeletal muscles is concerned, no difference in Hsp60 expression was found between wild‐type and mdx mice at any time in either gastrocnemius or quadriceps (Fig.…”

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus

“…In the brain, Hsp60 is expressed in astrocytes, neurons, microglia, oligodendrocytes, and ependymal cells (D'Souza & Brown, ), suggesting an active participation of this chaperonin in many functions of the brain both in normal and pathological conditions. Hsp60 is a mitochondrial protein constitutively expressed under normal conditions and induced by different types of stressors such as heat shock, oxidative stress, and DNA damage (Bukau & Horwich, ; Morici et al, , ; Parnas et al, ). Inside mitochondria, Hsp60 controls the correct folding of other mitochondrial proteins and mutations of Hsp60 cause cell death secondary to severe mitochondrial protein folding defects (Bross, Magnoni, & Bie, ).…”

DDAH1 Promotes Lung Endothelial Barrier Repair by Decreasing Leukocyte Transendothelial Migration and Oxidative Stress in Explosion-Induced Lung Injury

“…It attaches the extracellular matrix to the cytoskeleton through F-actin and participates in events of signaling and synaptic transmission. Morici et al found that a lack of dystrophin might impair the bronchial epithelium repair [ 37 ]. In this study, Evan's blue dye and the observed upregulation of VEGF, MMP9, N-cadherin, and vimentin demonstrated the increase of pulmonary vascular permeability and the occurrence of EMT.…”