title: Autocrine and immune cell-derived BDNF in human skeletal muscle: implications for myogenesis and tissue regeneration.
abstract: The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regeneration in vivo. However, the expression, localization and function of BDNF in human skeletal muscle tissue is not known, so the relevance of the rodent findings for human muscle are unknown. Here we address this by combining ex vivo histological investigations on human biopsies with in vitro analyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells both in vitro and in vivo. Differential analysis of BDNF receptors showed expression of p75NTR and not of TrkB in myocytes, suggesting that the BDNF-p75NTR axis is predominant in human skeletal muscle cells. Several in vitro functional experiments demonstrated that BDNF gene silencing or protein blockade in myoblast cultures hampered myogenesis. Finally, histological investigations of inflammatory myopathy biopsies revealed that infiltrating immune cells localized preferentially near p75NTR-positive regenerating fibres and that they produced BDNF. In conclusion, BDNF is an autocrine factor for skeletal muscle cells and may regulate human myogenesis. Furthermore, the preferential localization of BDNF-producing immune cells near p75NTR-positive regenerating myofibres suggests that immune cell-derived BDNF may sustain tissue repair in inflamed muscle.
authors.affiliation: Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.forename: Francesco
authors.initials: F
authors.lastname: Bedogni
authors.forename: Isabella
authors.initials: I
authors.lastname: Lorenzetti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Landsberger
authors.forename: Stefano C
authors.initials: SC
authors.lastname: Previtali
authors.forename: Cinthia
authors.initials: C
authors.lastname: Farina
mesh_terms: D000368:Aged; D019898:Autocrine Communication / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009220:Myositis / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C579455:BDNF protein, human
keywords: BDNF; human skeletal muscle; immune cells; inflammation; myogenesis; neurotrophin