title: β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.
abstract: We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, 05508-000, São Paulo, SP, Brazil.
authors.forename: Meiricris T
authors.initials: MT
authors.lastname: Silva
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, 05508-000, São Paulo, SP, Brazil.
authors.forename: Tábata L
authors.initials: TL
authors.lastname: Nascimento
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, 05508-000, São Paulo, SP, Brazil.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Pereira
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Adriane S
authors.initials: AS
authors.lastname: Siqueira
authors.affiliation: Department of Biodynamics, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Patrícia C
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Ruy G
authors.initials: RG
authors.lastname: Jaeger
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, 05508-000, São Paulo, SP, Brazil. elenm@usp.br.
authors.forename: Elen H
authors.initials: EH
authors.lastname: Miyabara
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D005786:Gene Expression Regulation; D006909:Hydroxyproline / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012038:Regeneration; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline
keywords: Collagen; Connective tissue repair; Metalloproteinase 9; Skeletal muscle regeneration; β2-Adrenoceptor