School of Kinesiology, Shanghai University of Sport, Shanghai, China.
School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
J Cell Physiol. 2020 Oct;235(10):6357-6365. doi: 10.1002/jcp.29600. Epub 2020 Jan 31.
C-type lectin domain family 11 member A (Clec11a), also known as stem cell growth factor (SCGF), C-type lectin superfamily member 3 (CLECSF3), or osteolectin was initially identified as a growth factor for hematopoietic progenitor cells. The human Clec11a gene encodes a polypeptide of 323 amino acids with characteristics of a secreted glycoprotein encompassing two integrin-binding motifs, RGD (Arg-Gly-Asp) and LDT (Leu-Asp-Thr), a putative leucine zipper domain, and a functional C-type lectin domain. It regulates hematopoietic differentiation and homeostasis and exhibits a protective effect against severe malarial anemia and lipotoxicity. Furthermore, Clec11a promotes the differentiation of mesenchymal progenitors into mature osteoblasts in vitro and plays an important role in the maintenance of adult skeleton age-related bone loss and fracture repair. Receptor ligand binding results in activation of downstream signaling cascades including glycogen synthase kinase 3 (GSK3), β-catenin, and Wnt, resulting in the expression of osteoblast-related gene transcripts including Alp, Runx2, Lef1, and Axin2. In addition, Clec11a is also associated with the development of several cancers, including leukemia, multiple myeloma, and gastrointestinal tract tumors. To date, however, the mechanisms governing transcription regulation of the Clec11a gene are not known and remain to be uncovered. Understanding the function and mechanism of action of Clec11a will pave the way for the development of Clec11a as a novel therapeutic target for conditions such as cancer, anemia, and skeletal diseases.
C 型凝集素结构域家族 11 成员 A（Clec11a），也称为干细胞生长因子（SCGF）、C 型凝集素超家族成员 3（CLECSF3）或骨粘连蛋白，最初被鉴定为造血祖细胞的生长因子。人类 Clec11a 基因编码一个由 323 个氨基酸组成的多肽，具有分泌糖蛋白的特征，包含两个整合素结合基序 RGD（精氨酸-甘氨酸-天冬氨酸）和 LDT（亮氨酸-天冬氨酸-苏氨酸）、一个推定的亮氨酸拉链结构域和一个功能性 C 型凝集素结构域。它调节造血分化和稳态，并表现出对严重疟疾贫血和脂肪毒性的保护作用。此外，Clec11a 促进间质祖细胞在体外向成熟成骨细胞分化，并在维持成人骨骼与年龄相关的骨丢失和骨折修复中发挥重要作用。受体配体结合导致下游信号级联的激活，包括糖原合酶激酶 3（GSK3）、β-连环蛋白和 Wnt，导致成骨相关基因转录物的表达，包括 Alp、Runx2、Lef1 和 Axin2。此外，Clec11a 还与几种癌症的发展有关，包括白血病、多发性骨髓瘤和胃肠道肿瘤。然而，目前尚不清楚调控 Clec11a 基因转录的机制，这仍然有待揭示。了解 Clec11a 的功能和作用机制将为将 Clec11a 开发为癌症、贫血和骨骼疾病等疾病的新型治疗靶点铺平道路。
