Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
FASEB J. 2022 Jul;36(7):e22389. doi: 10.1096/fj.202200317R.
The arginine-glycine-aspartic acid (RGD) motif is a cell adhesion sequence that binds to integrins. Some RGD-containing peptides promote adhesion of both embryonic stem cells and induced pluripotent stem cells (iPSCs); however, not all such RGD-containing peptides are active. In this study, we elucidated the role of RGD-neighboring sequences on iPSC adhesion using diverse synthetic peptides and recombinant proteins. Our results indicate that iPSC adhesion requires RGDX X sequences, such as RGDVF and RGDNY, and that the X X residues are essential for the adhesion via integrin αvβ5 but not αvβ3. iPSCs express integrin αvβ5 but not αvβ3; therefore, iPSC adhesion requires the RGDX X -containing sequences. The importance of the X X residues was confirmed with both HeLa and A549 cells, which express integrin αvβ5 but not αvβ3. Analysis of RGD-neighboring sequences provides important insights into ligand-binding specificity of integrins. Identification of integrin αvβ5-binding motifs is potentially useful in drug development, drug delivery, cell culture, and tissue engineering.
精氨酸-甘氨酸-天冬氨酸（RGD）基序是一种细胞黏附序列，与整合素结合。一些含有 RGD 的肽促进胚胎干细胞和诱导多能干细胞（iPSC）的黏附；然而，并非所有含有 RGD 的肽都是有效的。在这项研究中，我们使用各种合成肽和重组蛋白阐明了 RGD 邻近序列对 iPSC 黏附的作用。我们的结果表明，iPSC 黏附需要 RGDXX 序列，如 RGDVF 和 RGDNY，并且 XX 残基对于通过整合素 αvβ5 而不是 αvβ3 的黏附是必需的。iPSC 表达整合素 αvβ5 但不表达 αvβ3；因此，iPSC 黏附需要含有 RGDXX 序列的配体。通过 HeLa 和 A549 细胞（表达整合素 αvβ5 但不表达 αvβ3）进一步证实了 XX 残基的重要性。对 RGD 邻近序列的分析为整合素的配体结合特异性提供了重要的见解。鉴定整合素 αvβ5 结合基序在药物开发、药物输送、细胞培养和组织工程中具有潜在的用途。
