凝血级联的启动
中文名称
通路描述
凝血级联的启动阶段通过组织因子（TF）介导在带 TF 的细胞（如成纤维细胞、平滑肌细胞和周细胞）的细胞膜表面产生少量凝血酶（FIIa）。此外，激活的细胞（如极化巨噬细胞）和凋亡细胞，以及某些癌细胞，释放带有促凝血活性的 TF 携带的外泌体（EVs）（Hohensinner PJ et al., 2021; 综述：Hisada Y et al., 2022; Sachetto ATA et al., 2023）。TF 在静止细胞或 EV 的膜表面主要以隐式、促凝血活性无活性状态维持（Schecter AD et al. 1997; Bach RR 2006; Kothari H et al. 2013; Grover SP & Mackman N 2018）。在组织损伤或炎症时，TF 在膜表面转化为促凝血异构体。Ca²⁺依赖的磷脂酰丝氨酸（PS）暴露、鞘磷脂（SM）水解和 TF 内的硫 - 半胱氨酸交换协同促进 TF 在外质膜上的激活（Langer F & Ruf W 2014; Ansari SA et al. 2019）。激活的 TF 与循环血液接触，TF 的胞外部分与因子 VII（FVII）及其活性丝氨酸蛋白酶形式 FVIIa 以极高的亲和力和特异性结合（Vadivel K& Bajaj SP 2012; Prasad R & Sen P 2018）。TF:FVIIa 复合物通过转化 F 和 FX 的丝氨酸前体形式为活性蛋白酶 FIIa 和 FXa，后者参与凝血酶的产生。TF 异常表达与各种凝血病相关。例如，带 TF 的 EVs 的促凝血特性可能在癌症、脓毒症和感染等病理条件下促进血栓形成和弥散性血管内凝血（reviewed by Mackman N et al., 2021; Hisada Y et al., 2022; Sachetto ATA et al., 2023）。
英文描述
NPAS4 regulates expression of target genes NPAS4 is a basic helix loop helix (bHLH) transcription factor that needs to dimerize with another bHLH protein, either ARNT, ARNT2 or ARNTL, in order to be able to bind to target DNA (Ooe et al. 2004; Ooe et al. 2009).
NPAS4 is implicated as a transcriptional regulator of genes involved in neuronal development such as CDK5 (Yun et al. 2013), CDK5R1 (Yun et al. 2013), RBFOX3 (NeuN) (Yun et al. 2013), BDNF (Pruunsild et al. 2011) and RET (Sribudiani et al. 2011), genes involved in synaptogenesis and synaptic transmission such as NPTX2 (Lin et al. 2008), MDM2 (Yoshihara et al. 2014; Lv et al. 2021), FOS (Ramamoorthi et al. 2011), IQSEC3 (Kim et al. 2021), PLK2 (Weng et al. 2018) and possibly other genes (Lin et al. 2008; Shan et al. 2018), circadian rhythm-related genes such as NAMPT (West et al. 2013), and genes involved in neuroprotection upon injury such as GEM (Takahashi et al. 2021), SYT10 (Woitecki et al. 2016) and possibly other genes (Qiu et al. 2013). In pancreatic beta-cell, NPAS4 is implicated as a regulator of insulin synthesis under stress conditions (Sabatini et al. 2013).
The circadian clock regulated gene CRY1 was identified as NPAS4 target gene in sheep brain (West et al. 2013). The DBNL gene, encoding Drebrin, a dendrytic cytoskeleton modulator, was identified as a gene directly upregulated by Npas4 (Ooe et al. 2004)
NPAS4 is expressed in endothelial cells and may play a role in angiogenesis (Esser et al. 2017).
NPAS4 is implicated as a transcriptional regulator of genes involved in neuronal development such as CDK5 (Yun et al. 2013), CDK5R1 (Yun et al. 2013), RBFOX3 (NeuN) (Yun et al. 2013), BDNF (Pruunsild et al. 2011) and RET (Sribudiani et al. 2011), genes involved in synaptogenesis and synaptic transmission such as NPTX2 (Lin et al. 2008), MDM2 (Yoshihara et al. 2014; Lv et al. 2021), FOS (Ramamoorthi et al. 2011), IQSEC3 (Kim et al. 2021), PLK2 (Weng et al. 2018) and possibly other genes (Lin et al. 2008; Shan et al. 2018), circadian rhythm-related genes such as NAMPT (West et al. 2013), and genes involved in neuroprotection upon injury such as GEM (Takahashi et al. 2021), SYT10 (Woitecki et al. 2016) and possibly other genes (Qiu et al. 2013). In pancreatic beta-cell, NPAS4 is implicated as a regulator of insulin synthesis under stress conditions (Sabatini et al. 2013).
The circadian clock regulated gene CRY1 was identified as NPAS4 target gene in sheep brain (West et al. 2013). The DBNL gene, encoding Drebrin, a dendrytic cytoskeleton modulator, was identified as a gene directly upregulated by Npas4 (Ooe et al. 2004)
NPAS4 is expressed in endothelial cells and may play a role in angiogenesis (Esser et al. 2017).
所含基因
21 个基因