Department of Ophthalmology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Jinan, P.R. China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital, Shandong University, Jinan, China.
Stem Cells Dev. 2021 Mar;30(6):301-308. doi: 10.1089/scd.2020.0196. Epub 2021 Mar 1.
Secreted protein acidic and rich in cysteine (SPARC) shows a specific colocalization with limbal epithelial stem cells (LESCs) in vivo; however, the inherent relationship between SPARC and LESCs is still unclear. This study investigated the effects of SPARC on the maintenance of LESC stemness and corneal wound healing. To test the influence of different concentration of exogenous SPARC on the proliferation of LESCs, cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine staining were performed and the results indicated that 1 μg/mL SPARC was the optimum concentration for enhanced LESC proliferation. Compared with a control group, SPARC-treated group showed a higher expression of LESC-positive markers p63α, ABCG-2, and Bmi-1, and a lower level of differentiation marker cytokeratin-3 (CK3), thereby suggesting that SPARC could maintain LESC characteristic phenotype and suppress spontaneous epithelial differentiation in vitro. In vivo, exogenous SPARC accelerated the wound-healing process by both the enhancement of LESC proliferation and promoting the migration of the proliferating cells. However, the intact epithelium impaired this function of SPARC by contact inhibition.
富含半胱氨酸的酸性分泌蛋白(SPARC)在体内与角膜缘上皮干细胞(LESCs)表现出特异性共定位;然而,SPARC 和 LESCs 之间的内在关系尚不清楚。本研究探讨了 SPARC 对维持 LESC 干性和角膜伤口愈合的影响。为了测试不同浓度的外源性 SPARC 对 LESCs 增殖的影响,进行了细胞计数试剂盒-8 检测和 5-乙炔基-2'-脱氧尿苷染色,结果表明 1μg/ml SPARC 是增强 LESC 增殖的最佳浓度。与对照组相比,SPARC 处理组显示出 LESC 阳性标志物 p63α、ABCG-2 和 Bmi-1 的表达更高,分化标志物细胞角蛋白-3(CK3)的水平更低,这表明 SPARC 可以维持 LESC 的特征表型,并抑制体外自发的上皮分化。在体内,外源性 SPARC 通过增强 LESC 增殖和促进增殖细胞的迁移来加速伤口愈合过程。然而,完整的上皮通过接触抑制削弱了 SPARC 的这一功能。