Aby Katherine, Antony Ryan, Li Yifan
Department of Basic Biomedical Science, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Biology (Basel). 2023 Jun 24;12(7):903. doi: 10.3390/biology12070903.
Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor to BDNF, proBDNF, has an unknown role in skeletal muscle. The levels of proBDNF, mature BDNF, and their receptors were compared in the skeletal muscle and brain tissues of C57BL/6J mice. Tourniquet-induced hind limb ischemia-reperfusion injury was used to assess the function of skeletal muscle-derived proBDNF in skeletal muscle injury. Skeletal muscle-specific knockout of BDNF and pharmacological inhibition of p75NTR, the proBDNF receptor, were used to determine the role of proBDNF-p75NTR signaling. We show for the first time that proBDNF is the predominantly expressed form of BDNF in skeletal muscle and that proBDNF is significantly upregulated in skeletal muscle following hind limb ischemia-reperfusion injury. Skeletal muscle-specific knockout of BDNF blunted the inflammatory response in the injured tissue and appears to be mediated by the proBDNF-p75NTR pathway, as shown by the pharmacological inhibition of p75NTR. These findings suggest that skeletal muscle proBDNF plays a critical role in driving the inflammatory response following skeletal muscle injury.
脑源性神经营养因子（BDNF）已被证明在包括骨骼肌在内的许多非神经元组织中表达。骨骼肌BDNF在代谢和运动方面的功能已得到研究；然而，其在骨骼肌损伤中的作用却鲜为人知。BDNF的前体，即前体BDNF（proBDNF），在骨骼肌中的作用尚不清楚。比较了C57BL/6J小鼠骨骼肌和脑组织中proBDNF、成熟BDNF及其受体的水平。使用止血带诱导的后肢缺血再灌注损伤来评估骨骼肌源性proBDNF在骨骼肌损伤中的功能。通过骨骼肌特异性敲除BDNF以及对proBDNF受体p75NTR进行药理学抑制，来确定proBDNF-p75NTR信号传导的作用。我们首次表明，proBDNF是骨骼肌中BDNF的主要表达形式，并且在后肢缺血再灌注损伤后，骨骼肌中的proBDNF显著上调。如p75NTR的药理学抑制所示，骨骼肌特异性敲除BDNF可减弱损伤组织中的炎症反应，并且这似乎是由proBDNF-p75NTR途径介导的。这些发现表明，骨骼肌proBDNF在驱动骨骼肌损伤后的炎症反应中起关键作用。
