TGF-β3  (转化生长因子-β3)

TGF-β3 (转化生长因子-β3) 是执行许多细胞功能的 TGF-β 超家族亚群的成员。TGF-β3在胚胎发生和细胞分化中起作用。TGF-β3 在腭发生、伤口愈合过程中也起着关键作用。TGF-β3 能够直接与 II 型受体 (TβRII) 结合。在哺乳动物中发现了三种 TGF-β 异构体：TGF-β1、2 和 3，它们在结构和功能上都相似。TGF-β3 在胚胎发育、胚胎损伤的无疤痕修复、成人伤口愈合和组织稳态中很重要。它在调节细胞迁移、血管生成、上皮-间质转化、细胞凋亡、免疫功能调节、细胞外基质（ECM）产生和ECM重塑调节中具有重要作用；肿瘤生长和维持通常需要的生物学过程^[1][2]。
与该家族的所有成员一样，TGF-β3 在物种间高度保守，小鼠、大鼠和人类 TGF-β3 的序列同源性 >97%。
TGF-β3 通过整合素从 LAP 中释放出来：整合素结合导致 LAP 链的扭曲和随后释放活性 TGF-β3。TGF-β3 表达增加胎儿伤口愈合并减少纤连蛋白和胶原蛋白 I 和 III 的沉积，并且还改善新真皮的结构。成纤维细胞是伤口愈合过程中的关键细胞。此外，TGF-β3 实际上可能在包括皮肤、乳房、口腔和胃粘膜在内的一系列组织中对肿瘤发生起保护作用。与 TGF-β1 和 TGF-β2 相比，TGF-β3 是人类角质形成细胞中 DNA 合成的更有效抑制剂。TGF-β3 mRNA 在 CD4⁺ T 细胞、CD8⁺ T 细胞、γδT 细胞和 B 细胞等淋巴细胞中表达。 TGF-β3 具有通过抑制 B 细胞调节全身性自身免疫性疾病的潜力。此外，在腭发生过程中，TGF-β3 应该通过经典的 Smad 依赖性和非经典的 Smad 非依赖性信号转导信号。在人类 B 细胞中，TGF-β3 诱导 Smad1/5 以及 Smad2 和 Smad3磷酸化^[1][2][3] 。

TGF-β3 (transforming growth factor-β3) is a member of a TGF­beta superfamily subgroup that performs many cellular functions. TGF-β3 has a role in embryogenesis and cell differentiation. TGF-β3 also plays a critical role in palatogenesis, the wound healing process. TGF-β3 is capable of binding directly to the type II receptor (TβRII). Three TGF-β isoforms have been found in mammals: TGF-β1, 2, and 3, which are structurally and functionally similar. TGF-β3 is important in embryonic development, scarless repair of injury in the embryo, adult wound healing and tissue homeostasis. It has an important role in regulating cell migration, angiogenesis, epithelial-mesenchymal transition, apoptosis, modulation of immune function, extracellular matrix (ECM) production and the regulation of ECM remodelling; biological processes that are often required for tumour growth and maintenance^[1][2].
As with all members of the family, TGF-β3 is highly conserved across species, with mouse, rat and human TGF-β3 demonstrating >97% sequence homology.
TGF-β3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-β3. TGF-β3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis. Fibroblasts are key cells in the wound healing process. In addition, TGF-β3 may actually play a protective role against tumourigenesis in a range of tissues including the skin, breast, oral and gastric mucosa. TGF-β3 is a more potent inhibitor of DNA synthesis in human keratinocytes compared to TGF-β1 and TGF-β2. TGF-β3 mRNA is expressed in lymphocytes such as CD4⁺ T cells, CD8⁺ T cells, γδT cells, and B cells. TGF-β3 has the potential to regulate systemic autoimmune diseases by inhibiting B cells. Moreover, during palatogenesis, TGF-β3 is supposed to transduce signals via both canonical Smad-dependent and non-canonical Smad-independent signaling. In human B cells, TGF-β3 induces phosphorylation of Smad1/5 along with Smad2 and Smad3^[1][2][3].

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