Daneshvar Nasibeh, Anderson Judy E
Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada.
Front Cell Dev Biol. 2022 Jul 18;10:874756. doi: 10.3389/fcell.2022.874756. eCollection 2022.
Terminal Schwann cells (TSCs) help regulate the formation, maintenance, function, and repair of neuromuscular junctions (NMJs) and axon guidance after muscle injury. Premature activation of muscle satellite cells (SCs), induced by isosorbide dinitrate (ISDN) before injury, accelerates myogenic regeneration, disrupts NMJ remodeling and maturation, decreases Sema3A protein-induced neuro-repulsion, and is accompanied by time-dependent changes in S100B protein levels. Here, to study the effects of premature SC activation on TSCs and SCs, both expressing P75 nerve growth-factor receptor, hybridization was used to identify transcripts of S100B and Sema3A, and the number, intensity, and diameter of expression sites were analyzed. The number of sites/fields expressing S100B and Sema3A increased with regeneration time (both < 0.001). Expression-site intensity (S100B) and diameter (S100B and Sema3A) decreased during regeneration ( = 0.005; < 0.05, = 0.006, respectively). P75 protein colocalized with a subset of S100B and Sema3A expression sites. Principal component analyses of gene expression, protein levels, and histological variables (fiber diameter, vascular density) in control and ISDN-pretreated groups explained 83% and 64% of the dataset variance, respectively. A very strong loading coefficient for colocalization of P75 protein with S100B and Sema3A mRNAs (0.91) in control regenerating muscle dropped markedly during regeneration disrupted by premature SC activation (-0.10 in Factor 1 to 0.55 in Factor 3). These findings strongly implicate the triple-expression profile by TSCs and/or SCs as a strong correlate of the important synchrony of muscle and nerve regeneration after muscle tissue injury. The results have the potential to focus future research on the complex interplay of TSCs and SCs in neuromuscular tissue repair and help promote effective function after traumatic muscle injury.
终末施万细胞（TSCs）有助于调节神经肌肉接头（NMJs）的形成、维持、功能和修复以及肌肉损伤后的轴突导向。在损伤前由硝酸异山梨酯（ISDN）诱导的肌肉卫星细胞（SCs）过早激活，会加速肌源性再生，破坏NMJ重塑和成熟，降低Sema3A蛋白诱导的神经排斥作用，并伴有S100B蛋白水平随时间的变化。在此，为了研究过早的SCs激活对均表达P75神经生长因子受体的TSCs和SCs的影响，采用杂交技术鉴定S100B和Sema3A的转录本，并分析表达位点的数量、强度和直径。表达S100B和Sema3A的位点/视野数量随再生时间增加（均P<0.001）。再生过程中表达位点强度（S100B）和直径（S100B和Sema3A）降低（分别为P = 0.005；P<0.05，P = 0.006）。P75蛋白与一部分S100B和Sema3A表达位点共定位。对照和ISDN预处理组中基因表达水平、蛋白水平和组织学变量（纤维直径、血管密度）的主成分分析分别解释了数据集方差的83%和64%。在对照再生肌肉中，P75蛋白与S100B和Sema3A mRNA共定位的很强的负荷系数（0.91）在因过早SCs激活而破坏的再生过程中显著下降（从因子1中的-0.10降至因子3中的0.55）。这些发现有力地表明TSCs和/或SCs的三重表达谱是肌肉组织损伤后肌肉和神经再生重要同步性的强相关因素。这些结果有可能使未来的研究聚焦于TSCs和SCs在神经肌肉组织修复中的复杂相互作用，并有助于促进创伤性肌肉损伤后的有效功能恢复。
