Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder

Abstract

Introduction With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition. Methods Dystrophin distribution was evaluated in rat bladders by immunohistochemical colocalization with smooth muscle, interstitial, urothelial, and neuronal markers. Protein levels of Dp140, Dp71, and smooth muscle were quantitated by Western blotting of neonatal to adult rat bladders. Results Dystrophin colocalized with smooth muscle cells and afferent nerve fibers. Dp71 was expressed two‐ to threefold higher compared with Dp140, independently of age. Age‐related muscle mass changes did not influence isoform expression levels. Discussion Dystrophin is expressed in smooth muscle cells and afferent nerve fibers in the urinary bladder, which underscores that micturition problems in DMD may have not solely a myogenic but also a neurogenic origin. Muscle Nerve 60: 202–210, 2019

Proteomic profiling of the interface between the stomach wall and the pancreas in dystrophinopathy

“…The detailed proteomic analysis of the interface between the stomach wall and the pancreas confirmed previous biochemical and cell biological studies that have shown the presence of both dystrophin 10,11 and dystrophinassociated proteins [18][19][20] in smooth muscle cells. Dystrophin exists in various tissue-specific isoforms with the largest proteoforms of apparent 427 kDa being mostly expressed in muscle cells and the nervous system.…”

“…In contrast to the usually positive effects of immune cell infiltration during muscle repair mechanisms following an acute injury, the chronic inflammatory phenotype of dystrophin-deficient muscle fibres appears to be mostly detrimental. 9 Dystrophin was previously established to be present in all muscle cell types, 10 including smooth muscles, 11 and dystrophinopathies were shown to be associated with gastrointestinal dysfunction. 4,5,[12][13][14][15] Thus, to investigate whether the smooth muscle protein constituents of the gastrointestinal system are majorly affected by dystrophin deficiency, we carried out a mass spectrometry-based proteomic analysis of the established genetic mdx-4cv mouse model of Duchenne muscular dystrophy, which also displays considerable abnormalities in the gastrointestinal system.…”

Presentation and Management Patterns of Lower Urinary Tract Symptoms in Adults Due to Rare Inherited Neuromuscular Diseases

“…A recent study found that dystrophin is expressed in smooth muscle cells and afferent nerve fibers in rat urinary bladders, meaning that micturition problems in MD may have both a myogenic and neurogenic component. 2 A better understanding of the pathogenesis of urinary difficulties is needed in this population as myopathic involvement of the detrusor would be expected to decrease the strength of bladder contractions and cause a large capacity, flaccid bladder, which was not observed in either study. 16 Very limited data exist regarding urologic issues in those with SMA.…”

“…Dystrophin expression has even been found in some nerves, including afferent nerves of the bladder. 2 The 2 most common forms, Duchenne MD (DMD) and Becker MD (BMD) are caused by 2 different inherited defects in the DMD gene (Xp21.2) responsible for the production of dystrophin. 3 Women are carriers with variable penetrance and men are more severely affected.…”

Urinary incontinence in men with Duchenne and Becker muscular dystrophy

“…It is however apparent that despite skeletal muscle weakness being a primary clinical sign, the impact of D/BMD on smooth muscle may contribute to the presentation of co-morbidities, particularly within the urinary tract [6]. In boys with DMD, there is a 50% prevalence of lower urinary tract symptoms (LUTS) [7], which could in part be linked to the expression of dystrophin within the smooth muscle of the bladder and upper urinary tract [8]. Ambiguity surrounding the reporting of LUTS (i.e.…”