Expression of myogenic regulatory factors and myo-endothelial remodeling in sporadic inclusion body myositis.
Muscle repair relies on coordinated activation and differentiation of satellite cells, a process that is unable to counterbalance progressive degeneration in sporadic inclusion body myositis (s-IBM). To explore features of myo regeneration, the expression of myogenic regulatory factors Pax7, MyoD and Myogenin and markers of regenerating fibers was analyzed by immunohistochemistry in s-IBM muscle compared with polymyositis, dermatomyositis, muscular dystrophy and age-matched controls. In addition, the capillary density and number of interstitial CD34(+) hematopoietic progenitor cells was determined by double-immunoflourescence staining. Satellite cells and regenerating fibers were significantly increased in s-IBM similar to other inflammatory myopathies and correlated with the intensity of inflammation (R>0.428). Expression of MyoD, visualizing activated satellite cells and proliferating myoblasts, was lower in s-IBM compared to polymyosits. In contrast, Myogenin a marker of myogenic cell differentiation was strongly up-regulated in s-IBM muscle. The microvascular architecture in s-IBM was distorted, although the capillary density was normal. Notably, CD34(+) hematopoietic cells were significantly increased in the interstitial compartment. Our findings indicate profound myo-endothelial remodeling of s-IBM muscle concomitant to inflammation. An altered expression of myogenic regulatory factors involved in satellite cell activation and differentiation, however, might reflect perturbations of muscle repair in s-IBM.
Clinical Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Austria. julia.wanschitz@i-med.ac.at
Julia V
JV
Wanschitz
Odile
O
Dubourg
Emmanuelle
E
Lacene
Michael B
MB
Fischer
Romana
R
Höftberger
Herbert
H
Budka
Norma B
NB
Romero
Bruno
B
Eymard
Serge
S
Herson
Gillian S
GS
Butler-Browne
Thomas
T
Voit
Olivier
O
Benveniste
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D003882:Dermatomyositis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004727:Endothelium / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017570:MyoD Protein / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051763:PAX7 Transcription Factor / Q000378:metabolism; D017285:Polymyositis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012038:Regeneration; D055815:Young Adult
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human