Morphological and ultrastructural evaluation of the golden retriever muscular dystrophy trachea, lungs, and diaphragm muscle

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disease, characterized by atrophy and muscle weakness. The respiratory failure is a common cause of early death in patients with DMD. Golden retriever muscular dystrophy (GRMD) is a canine model which has been extensively used for many advances in therapeutics applications. As the patients with DMD, the GRMD frequently died from cardiac and respiratory failure. Observing the respiratory failure in DMD is one of the major causes of mortality we aimed to describe the morphological and ultrastructural data of trachea, lungs (conductive and respiratory portion of the system), and diaphragm muscle using histological and ultrastructural analysis. The diaphragm muscle showed discontinuous fibers architecture, with different diameter; a robust perimysium inflammatory infiltrate and some muscle cells displayed central nuclei. GRMD trachea and lungs presented collagen fibers and in addition, the GRMD lungs showed higher of levels collagen fibers that could limit the alveolar ducts and alveoli distension. Therefore, the most features observed were the collagen areas and fibrosis. We suggested in this study that the collagen remodeling in the trachea, lungs, and diaphragm muscle may increase fibrosis and affect the trachea, lungs, and diaphragm muscle function that can be a major cause of respiratory failure that occur in patients with DMD.

Concurrent Label-Free Mass Spectrometric Analysis of Dystrophin Isoform Dp427 and the Myofibrosis Marker Collagen in Crude Extracts from mdx-4cv Skeletal Muscles

“…This makes changes in the extracellular matrix surrounding dystrophic fibers a robust myopathological characteristic of X-linked muscular dystrophy. In analogy to the fact that muscle-derived fibroblasts from Duchenne patients show signs of a pro-fibrotic phenotype and an enhanced proliferation rate coupled to the increased production of collagens [84,85], fibrotic changes are also observed in animal models of muscular dystrophy [86,87,88,89]. Since fibrosis is intrinsically involved in the molecular pathogenesis of muscular dystrophy, systematic studies of global protein changes in dystrophic fibers should be able to correlate the deficiency in dystrophin with altered expression levels of key components of the extracellular matrix [37].…”

Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

“…Four mechanisms could explain the low C rs in individuals with RMW: atelectasis [1, 3], stiffening of the lung tissue [33], ankylosis of the costosternal and costovertebral joints [8] and increasing alveolar surface forces [34, 35]. Presumably, LVR serves to temporarily mitigate the influence of one or several of the aforementioned factors.…”

Respiratory impedance in patients with Duchenne muscular dystrophy

“…29 If this abnormalities also occur in lung fibroblasts, then the composition of the pulmonary interstitium might be different in patients with DMD, potentially affecting its elastic properties (and hence, reactances), as has been shown in animal models. 30 On the other hand, because dystrophin is also expressed in vascular smooth muscle and endothelium, changes in the vascular morphology (including angiogenesis, as observed in animal models 31 ) and vascular permeability (producing edema, as observed in DMD skeletal muscle 32 ), if occurring in the lung, might also change the mechanical properties of the lung parenchyma.…”