THBS2（血小板反应蛋白2，Thrombospondin 2）属于血小板反应蛋白（Thrombospondin，TSP）基因家族，该家族包含5个成员（TSP1-5），共同特点是编码分泌型糖蛋白，参与细胞间相互作用、细胞黏附、血管生成及组织重塑等过程。THBS2蛋白由多个功能域组成，包括N端结构域、Ⅲ型重复序列（与钙结合相关）和C端结构域，能结合细胞表面受体（如CD36、整合素）及基质分子（如胶原、纤连蛋白），调控细胞迁移、增殖和凋亡。其生物学功能主要包括抑制血管生成（通过阻断VEGF信号）、调节细胞外基质（ECM）组装及免疫调节（如调控巨噬细胞极化）。在胚胎发育中，THBS2对心血管和骨骼系统形成至关重要。THBS2突变可能导致功能丧失，与结缔组织异常（如Ehlers-Danlos综合征样症状）或血管畸形相关。该基因在多种癌症（如乳腺癌、胃癌）中表达下调，其抑癌作用与抑制肿瘤血管生成和转移有关；而过表达THBS2可能通过增强ECM稳定性抑制肿瘤侵袭。THBS2表达降低会促进血管过度生长（如糖尿病视网膜病变）或组织纤维化（如肝纤维化），而过高表达可能阻碍组织修复（如伤口愈合延迟）。THBS家族共性在于均含保守的Ⅲ型重复序列和C端结构域，但THBS1/2形成亚组，具有抗血管生成特性，而THBS4/5主要作用于神经系统发育。THBS2与炎症性疾病（如关节炎）也相关，其表达受TGF-β等生长因子调控，并能影响MMP（基质金属蛋白酶）的活性，进一步调节ECM动态平衡。

由该基因编码的蛋白质属于血小板家族。它是一个二硫键连接的同源三聚体糖蛋白，其介导细胞 - 细胞和细胞 - 基质相互作用。这种蛋白已经显示出作为肿瘤生长和血管生成的有效抑制剂。鼠标对方的研究表明，这种蛋白质可调节的间充质细胞的细胞表面性质并参与细胞的粘附和迁移。 [由RefSeq的，2008年7月提供]

The THBS2 gene encodes Thrombospondin 2, a secreted glycoprotein belonging to the thrombospondin family, which comprises five members (TSP1–5) characterized by conserved structural motifs including N-terminal domains, calcium-binding type III repeats, and C-terminal domains that facilitate interactions with cell surface receptors such as CD36 and integrins, as well as extracellular matrix (ECM) components like collagen and fibronectin. These structural features enable THBS2 to modulate critical cellular processes, including migration, proliferation, and apoptosis, while exerting significant anti-angiogenic effects by inhibiting vascular endothelial growth factor (VEGF) signaling and regulating ECM assembly. Beyond its role in vascular homeostasis, THBS2 participates in immune regulation by influencing macrophage polarization and modulating the activity of matrix metalloproteinases (MMPs), thereby maintaining the dynamic balance of the ECM under the regulatory influence of growth factors such as TGF-β. While distinct from its family members THBS4 and THBS5, which are primarily involved in nervous system development, THBS2 forms a functional subgroup with THBS1 that is particularly notable for its potent anti-angiogenic properties, a trait that is crucial during embryonic cardiovascular and skeletal development. In the context of human disease, loss-of-function mutations in THBS2 can lead to connective tissue disorders resembling Ehlers-Danlos syndrome or vascular malformations, whereas dysregulated expression levels have broad pathological implications: downregulation is frequently observed in various malignancies, such as breast and gastric cancers, where it may contribute to tumor progression by failing to suppress angiogenesis and metastasis, although overexpression can paradoxically inhibit tumor invasion by enhancing ECM stability. Furthermore, altered THBS2 expression is implicated in inflammatory and fibrotic conditions, where decreased levels may promote pathological vascular growth in diabetic retinopathy or contribute to liver fibrosis, while excessive expression can impair tissue repair mechanisms, leading to delayed wound healing and exacerbating inflammatory states in conditions like arthritis.

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