CCL14  (趋化因子 CCL14)

CCL14 又称 HCC-1，一种人血浆趋化因子，最初是从慢性肾功能衰竭患者的血滤液中收集并纯化的。CCL14属于 CC趋化因子家族的小细胞因子，位于人类 17 号染色体上的趋化因子簇，可以在各种组织中表达，包括脾脏、骨髓、肝脏、肌肉和肠道。CCL14 对人类单核细胞具有弱活性，而对 T 淋巴细胞、中性粒细胞和嗜酸性白细胞无活性。CCL14 作为一种蛋白质前体，需要经过蛋白水解处理以获得受体亲和力，其经加工可产生含有 74 个氨基酸的成熟活性蛋白质。加工后得到的 HCC-1(9-74) 是一种趋化因子，可吸引单核细胞、嗜酸性粒细胞和 T 细胞，可以与 CCR1、CCR3 和 CCR5 趋化因子受体结合^[2]。CCL14 趋化因子经翻译后修饰，如 N 末端截短，糖基化等，与未修饰的相比，其信号传导也会产生差异。例如，全长 CCL14(1-74) 和截断异构体CCL14（9-74）都能与非典型趋化因子受体2（ACKR2）结合，但与 CCL14（1-74）相比，只有截断的CCL14（9-74）显示出 β-restin 的倾向性，并能诱导 ACKR2 的受体内化。与此同时，CCL14(1-74) 是趋化因子受体 CCR1 的弱激动剂，但其活性在蛋白水解切割为 CCL14(9-74) 后显着增强^[1]。 研究表明，CCL14 可以通过抑制细胞周期进程和促进肝细胞癌 (HCC) 细胞凋亡来抑制 HCC 细胞增殖。CCL14 在体内抑制裸鼠体内 HCC 的肿瘤生长。CCL14 还参与各种疾病的发病机制和进展，包括过敏性气道炎症和一些癌症^[2]。

CCL14, also known as HCC-1, is a human plasma chemokine originally collected and purified from the hemofiltrate of patients with chronic renal failure. CCL14 belongs to the small cytokine family of CC chemokines, a cluster of chemokines located on human chromosome 17 that can be expressed in a variety of tissues, including spleen, bone marrow, liver, muscle, and intestine. CCL14 has weak activity against human monocytes and no activity against T lymphocytes, neutrophils, and eosinophils. CCL14 is weakly active against human monocytes and inactive against T lymphocytes, neutrophils, and eosinophils.CCL14 acts as a protein precursor that requires protein hydrolysis to obtain receptor affinity and is processed to yield a mature active protein containing 74 amino acids. The processed HCC-1(9-74) is a chemokine that attracts monocytes, eosinophils and T cells and binds to CCR1, CCR3 and CCR5 chemokine receptors^[2]. Post-translational modifications of CCL14 chemokines, such as N-terminal truncation and glycosylation, also result in differential signaling compared to unmodified ones. For example, both full-length CCL14(1-74) and truncated isoform CCL14(9-74) bind to atypical chemokine receptor 2 (ACKR2), but only truncated CCL14(9-74) shows a propensity for β-restin and induces receptor internalization of ACKR2 compared to CCL14(1-74). Meanwhile, CCL14(1-74) was a weak agonist of chemokine receptor CCR1, but its activity was significantly enhanced after proteolytic cleavage to CCL14(9-74)^[1]. CCL14 has been shown to inhibit HCC cell proliferation by inhibiting cell cycle progression and promoting apoptosis in hepatocellular carcinoma (HCC) cells.CCL14 inhibits HCC tumor growth in nude mice in vivo.CCL14 is also involved in the pathogenesis and progression of various diseases, including allergic airway inflammation and some cancers^[2].

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