ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation.
ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation.
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DOI：
10.3390/biology12070903
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发表时间：
2023-06-24
期刊：
影响因子：
4.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Aby K;Antony R;Li Y
骨骼肌缺血再灌注损伤是常见的，但其机制还不清楚。此外，脑源性神经营养因子及其前体在骨骼肌中的作用尚未确定。为了解决这一问题，本研究旨在探讨前脑源性神经营养因子在后肢缺血再灌注损伤中的作用。研究表明，脑源性神经营养因子前体在损伤后骨骼肌中显著上调，并且在缺乏骨骼肌脑源性神经营养因子前体信号传导的情况下，炎症反应显著减弱。总的结论是，前脑源性神经营养因子是必不可少的缺血再灌注损伤后的炎症反应。脑源性神经营养因子（BDNF）已被证明在许多非神经元组织包括骨骼肌中表达。骨骼肌BDNF在代谢和运动中的作用已被研究;然而，对其在骨骼肌损伤中的作用知之甚少。BDNF的前体，proBDNF，在骨骼肌中的作用尚不清楚。比较C57 BL/6 J小鼠骨骼肌和脑组织中proBDNF、成熟BDNF及其受体的水平。采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在骨骼肌损伤中的作用。使用骨骼肌特异性敲除BDNF和药理学抑制p75 NTR（proBDNF受体）来确定proBDNF-p75 NTR信号传导的作用。我们首次表明，proBDNF是BDNF在骨骼肌中的主要表达形式，并且proBDNF在后肢缺血再灌注损伤后骨骼肌中显著上调。骨骼肌特异性敲除BDNF减弱了损伤组织中的炎症反应，并且似乎是由proBDNF-p75 NTR通路介导的，如p75 NTR的药理学抑制所示。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着关键作用。
Ischemia reperfusion injury in skeletal muscle is common, yet the underlying mechanisms are not well understood. Additionally, the role of brain-derived neurotrophic factor and its precursor in skeletal muscle have not been determined. To address this, the present study aimed to investigate the role of pro-brain-derived neurotrophic factor in ischemia reperfusion injury of the hind limb. It was shown that pro-brain-derived neurotrophic factor is significantly upregulated in skeletal muscle following injury, and that in the absence of skeletal muscle pro-brain-derived-neurotrophic factor signaling, the inflammatory response was significantly blunted. The overall conclusion is that pro-brain-derived neurotrophic factor is essential to the inflammatory response following ischemia reperfusion injury. 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.
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DOI：
10.1073/pnas.1900544116
发表时间：
2019-08-06
影响因子：
11.1
作者：
Delezie, Julien;Weihrauch, Martin;Handschin, Christoph
通讯作者：
Handschin, Christoph
外周脑源性神经营养因子前体作为炎症介质调节疼痛
影响因子：
4.6
作者：
Luo C;Zhong XL;Zhou FH;Li JY;Zhou P;Xu JM;Song B;Li CQ;Zhou XF;Dai RP
通讯作者：
Dai RP
DOI：
10.1161/atvbaha.120.315028
发表时间：
2020-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Lee JJ;Arpino JM;Yin H;Nong Z;Szpakowski A;Hashi AA;Chevalier J;O'Neil C;Pickering JG
通讯作者：
Pickering JG
影响因子：
7.3
作者：
Colombo, Emanuela;Bedogni, Francesco;Farina, Cinthia
通讯作者：
Farina, Cinthia
影响因子：
4.6
作者：
Chopra, Anand;Willmore, William G.;Biggar, Kyle K.
通讯作者：
Biggar, Kyle K.