Myogenic precursor cells differentially participate in vascular remodeling in Juvenile Dermatomyositis and Duchenne Muscular Dystrophy

ABSTRACT: Skeletal muscle is highly vascularized. Beyond oxygen and nutriment supply, new functions for vessels have been recently identified, via the interactions that vessel cells establish with muscle progenitor cells. These latter cells closely interact with endothelial cells for their expansion and their differentiation, while periendothelial cells are involved in muscle cell self-renewal and return to quiescence. Thus, vessels play a central role in the tissue remodeling after an injury, while the mechanisms are poorly understood. We investigated myogenic/endothelial cell (MPCs/ECs) interactions in two paradigmatic contexts of regenerating muscle in the child: Juvenile Dermatomyositis (JDM), which is characterized by a transient loss of capillaries, and Duchenne Muscular Dystrophy (DMD), which is associated with an increase in vessel density. We showed in vitro specific interactions between myoblasts isolated from muscle of JDM and DMD patients and endothelial cells. In vitro myogenesis/angiogenesis studies demonstrated that MPCs exhibited various angiogenic properties depending on the pathological environment. In DMD, MPCs promoted the development of an anarchic, although strong, ECs stimulation, leading to the formation of weakly functional vessels. DMD cells presented an unbalanced homeostasis with nonspecific deregulation of several processes involved in muscle and vessel development. On the contrary, in JDM, MPCs enhanced the vessel reconstruction to efficiently restore the vessel function via the expression of a set of specific angiogenic effectors. MPCs exhibit a strong specific type I IFNs signature and ECs a dysregulation of their angiogenic capacities, suggesting a drastic reprogrammation of these cells in response to an inflammatory environment during JDM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66845 | GEO | 2017/07/27

SECONDARY ACCESSION(S): PRJNA278077

REPOSITORIES: GEO