title: CD13 regulates anchorage and differentiation of the skeletal muscle satellite stem cell population in ischemic injury.
abstract: CD13 is a multifunctional cell surface molecule that regulates inflammatory and angiogenic mechanisms in vitro, but its contribution to these processes in vivo or potential roles in stem cell biology remains unexplored. We investigated the impact of loss of CD13 on a model of ischemic skeletal muscle injury that involves angiogenesis, inflammation, and stem cell mobilization. Consistent with its role as an inflammatory adhesion molecule, lack of CD13 altered myeloid trafficking in the injured muscle, resulting in cytokine profiles skewed toward a prohealing environment. Despite this healing-favorable context, CD13(KO) animals showed significantly impaired limb perfusion with increased necrosis, fibrosis, and lipid accumulation. Capillary density was correspondingly decreased, implicating CD13 in skeletal muscle angiogenesis. The number of CD45-/Sca1-/α7-integrin+/β1-integrin+ satellite cells was markedly diminished in injured CD13(KO) muscles and adhesion of isolated CD13(KO) satellite cells was impaired while their differentiation was accelerated. Bone marrow transplantation studies showed contributions from both host and donor cells to wound healing. Importantly, CD13 was coexpressed with Pax7 on isolated muscle-resident satellite cells. Finally, phosphorylated-focal adhesion kinase and ERK levels were reduced in injured CD13(KO) muscles, consistent with CD13 regulating satellite cell adhesion, potentially contributing to the maintenance and renewal of the satellite stem cell pool and facilitating skeletal muscle regeneration.
authors.affiliation: Center for Vascular Biology and University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: M Mamunur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Mallika
authors.initials: M
authors.lastname: Ghosh
authors.forename: Jaganathan
authors.initials: J
authors.lastname: Subramani
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Fong
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Carlson
authors.forename: Linda H
authors.initials: LH
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D018826:CD13 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing
chemical_list: D016207:Cytokines; D018826:CD13 Antigens
keywords: Angiogenesis; CD13; Hind limb ischemia; Muscle stem cells