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Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1?-controlled BNP.

ABSTRACT: Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-activated receptor ? co-activator 1? (PGC-1?) also has a profound effect on cytokine expression in muscle tissue. Muscle PGC-1? expression results in activation of tissue-resident macrophages, at least in part mediated by PGC-1?-dependent B-type natriuretic peptide (BNP) production and secretion. Positive effects of exercise in metabolic diseases and other pathologies associated with chronic inflammation could accordingly involve the PGC-1?-BNP axis and thereby provide novel targets for therapeutic approaches.

SUBMITTER: Furrer R

PROVIDER: S-EPMC5238507 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP.

Furrer Regula R Eisele Petra S PS Schmidt Alexander A Beer Markus M Handschin Christoph C

Scientific reports 20170116

Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-acti ...[more]

PMID: 28091624

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Project description:RationaleMechanisms of angiogenesis in skeletal muscle remain poorly understood. Efforts to induce physiological angiogenesis hold promise for the treatment of diabetic microvascular disease and peripheral artery disease but are hindered by the complexity of physiological angiogenesis and by the poor angiogenic response of aged and patients with diabetes mellitus. To date, the best therapy for diabetic vascular disease remains exercise, often a challenging option for patients with leg pain. Peroxisome proliferation activator receptor-γ coactivator-1α (PGC-1α), a powerful regulator of metabolism, mediates exercise-induced angiogenesis in skeletal muscle.ObjectiveTo test whether, and how, PGC-1α can induce functional angiogenesis in adult skeletal muscle.Methods and resultsHere, we show that muscle PGC-1α robustly induces functional angiogenesis in adult, aged, and diabetic mice. The process involves the orchestration of numerous cell types and leads to patent, nonleaky, properly organized, and functional nascent vessels. These findings contrast sharply with the disorganized vasculature elicited by induction of vascular endothelial growth factor alone. Bioinformatic analyses revealed that PGC-1α induces the secretion of secreted phosphoprotein 1 and the recruitment of macrophages. Secreted phosphoprotein 1 stimulates macrophages to secrete monocyte chemoattractant protein-1, which then activates adjacent endothelial cells, pericytes, and smooth muscle cells. In contrast, induction of PGC-1α in secreted phosphoprotein 1(-/-) mice leads to immature capillarization and blunted arteriolarization. Finally, adenoviral delivery of PGC-1α into skeletal muscle of either young or old and diabetic mice improved the recovery of blood flow in the murine hindlimb ischemia model of peripheral artery disease.ConclusionsPGC-1α drives functional angiogenesis in skeletal muscle and likely recapitulates the complex physiological angiogenesis elicited by exercise.

Dataset Information

Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1?-controlled BNP.

Publications

Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP.

Similar Datasets

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