Functions and mechanisms of action of CCN matricellular proteins.
Functions and mechanisms of action of CCN matricellular proteins.
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DOI：
10.1016/j.biocel.2008.07.025
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发表时间：
2009-04
影响因子：
4
通讯作者：
Lau, Lester F.
中科院分区：
文献类型：
--
作者：
Chen, Chih-Chiun;Lau, Lester F.
CCN(CYR61/CTGF/NOV)家族的成员作为动态表达的细胞外基质相关蛋白出现，在心血管和骨骼发育、损伤修复、纤维化疾病和癌症中发挥关键作用。CCN蛋白的合成受血清生长因子、细胞因子和环境应激(如低氧、紫外线照射和机械拉伸)的高度诱导。CCNS由脊椎动物中的六种分泌蛋白组成，通常由四个保守的富含半胱氨酸的模块结构域组成。它们的功能主要是通过与特定的整合素受体和硫酸乙酰肝素蛋白多糖直接结合，从而触发信号转导事件，最终调控细胞的黏附、迁移、增殖、基因表达、分化和生存。CCN蛋白还可以调节几种生长因子和细胞因子的活性，包括转化生长因子-β、肿瘤坏死因子α、血管内皮生长因子、骨形态发生蛋白和WNT蛋白，从而可能调节广泛的生物过程。最近的研究发现了母细胞蛋白意想不到的新的CCN活性，包括它们作为细胞黏附底物诱导细胞凋亡的能力，决定炎症细胞因子如肿瘤坏死因子α的细胞毒性，以及促进造血干细胞的自我更新。作为血管生成和软骨生成的有效调节因子，CCNS在胚胎发育过程中对心血管和骨骼的成功发育至关重要。在成人中，CCN蛋白的表达与损伤修复和炎症有关，已被认为是糖尿病肾病、肝纤维化、系统性硬化症和几种癌症的诊断或预后标志物。靶向CCN信号通路有望成为一种合理的治疗设计策略。
Members of the CCN (CYR61/CTGF/NOV) family have emerged as dynamically expressed, extracellular matrix-associated proteins that play critical roles in cardiovascular and skeletal development, injury repair, fibrotic diseases and cancer. The synthesis of CCN proteins is highly inducible by serum growth factors, cytokines, and environmental stresses such as hypoxia, UV exposure, and mechanical stretch. Consisting of six secreted proteins in vertebrate species, CCNs are typically comprised of four conserved cysteine-rich modular domains. They function primarily through direct binding to specific integrin receptors and heparan sulfate proteoglycans, thereby triggering signal transduction events that culminate in the regulation of cell adhesion, migration, proliferation, gene expression, differentiation, and survival. CCN proteins can also modulate the activities of several growth factors and cytokines, including TGF-β, TNFα, VEGF, BMPs, and Wnt proteins, and may thereby regulate a broad array of biological processes. Recent studies have uncovered novel CCN activities unexpected for matricellular proteins, including their ability to induce apoptosis as cell adhesion substrates, to dictate the cytotoxicity of inflammatory cytokines such as TNFα, and to promote hematopoietic stem cell self-renewal. As potent regulators of angiogenesis and chondrogenesis, CCNs are essential for successful cardiovascular and skeletal development during embryogenesis. In the adult, the expression of CCN proteins is associated with injury repair and inflammation, and has been proposed as diagnostic or prognostic markers for diabetic nephropathy, hepatic fibrosis, systemic sclerosis, and several types of cancer. Targeting CCN signaling pathways may hold promise as a strategy of rational therapeutic design.
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影响因子：
4.8
作者：
Chen, CC;Mo, FE;Lau, LF
通讯作者：
Lau, LF
影响因子：
4.8
作者：
Chen, CC;Chen, NY;Lau, LF
通讯作者：
Lau, LF
DOI：
10.1073/pnas.95.11.6355
发表时间：
1998-05-26
影响因子：
11.1
作者：
Babic, AM;Kireeva, ML;Lau, LF
通讯作者：
Lau, LF
影响因子：
5.7
作者：
Aikawa, Takuma;Gunn, Jason;Korc, Murray
通讯作者：
Korc, Murray
DOI：
10.1083/jcb.114.6.1285
发表时间：
1991-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bradham DM;Igarashi A;Potter RL;Grotendorst GR
通讯作者：
Grotendorst GR