association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans协会的白细胞介素- 6与肌肉干细胞信号响应muscle-lengthening收缩后人类.pdf

Association of Interleukin-6 Signalling with the Muscle Stem Cell Response Following Muscle-Lengthening Contractions in Humans 1 1 1 1 1 Bryon R. McKay , Michael De Lisio , Adam P. W. Johnston , Ciara E. O’Reilly , Stuart M. Phillips , Mark A. Tarnopolsky2, Gianni Parise1,3* 1 Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada, 2 Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada, 3 Department of Medical Physics Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada Abstract Background: The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC) response following muscle-lengthening contractions in humans has not been studied. Methodology/Principal Findings: Eight subjects (age 2261 y; 7968 kg) performed 300 maximal unilateral lengthening contractions (3.14 rad.s21) of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor (IL-6Ra), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7+ cells) as well as the expression of phosphorylated STAT3, IL-6, IL-6Ra, and PCNA across all time-points. The SC