Laminin-511 Activates the Human Induced Pluripotent Stem Cell Survival via α6β1 Integrin-Fyn-RhoA-ROCK Signaling

In human induced pluripotent stem cells (hiPSCs), laminin-511/α6β1 integrin interacts with E-cadherin, an intercellular adhesion molecule, to induce the activation of the phosphatidylinositol 3-kinase (PI3K) -dependent signaling pathway. The interaction between laminin-511/α6β1 integrin and E-cadherin, an intercellular adhesion molecule, results in protection against apoptosis through the proto-oncogene tyrosine-protein kinase Fyn (Fyn) -RhoA-ROCK signaling pathway and the Ras homolog gene family member A (RhoA) /Rho kinase (ROCK) signaling pathway (the major pathway for cell death). In this article, the impact of laminin-511 on hiPSC on α6β1 integrin-Fyn-RhoA-ROCK signaling is discussed and explored along with validation experiments. PIK3CA mRNA (mean standard deviation SD: iMatrix-511, 1. 00 0. 61; collagen+MFGE8, 0. 023 0. 02; ** P < 0. 01; n = 6) and PIK3R1 mRNA (mean SD: iMatrix-511, 1. 00 0. 79; collagen+MFGE8, 0. 040 0. 06; * P < 0. 05; n = 6) were upregulated by iMatrix-511 resulting from an increased expression of Integrin α6 mRNA (mean SD: iMatrix-511, 1. 00 0. 42; collagen+MFGE8, 0. 23 0. 05; ** P < 0. 01; n = 6). The iMatrix-511 increased the expression of p120- Catenin mRNA (mean SD: iMatrix-511, 1. 00 0. 71; collagen+MFGE8, 0. 025 0. 03; ** P < 0. 01; n = 6) and RAC1 mRNA (mean SD: iMatrix-511, 1. 00 0. 28; collagen+MFGE8, 0. 39 0. 15; ** P < 0. 01; n = 6) by increasing the expression of E-cadherin mRNA (mean SD: iMatrix-511, 1. 00 0. 38; collagen+MFGE8, 0. 16 0. 11; ** P < 0. 01; n = 6). As a result, iMatrix-511 increased the expression of P190 RhoGAP (GTPase-activating proteins) mRNA, such as ARHGAP1 mRNA (mean SD: iMatrix-511, 1. 00 0. 57; collagen+MFGE8, 0. 032 0. 03; ** P < 0. 01; n = 6), ARHGAP4 mRNA (mean SD: iMatrix-511, 1. 00 0. 56; collagen+MFGE8, 0. 039 0. 049; ** P < 0. 01; n = 6), and ARHGAP5 mRNA (mean SD: iMatrix-511, 1. 00 0. 39; collagen+MFGE8, 0. 063 0. 043; ** P < 0. 01; n = 6). Western blotting showed that phospho-Rac1 remained in the cytoplasm and phospho-Fyn showed nuclear transition in iPSCs cultured on iMatrix-511. Proteome analysis showed that PI3K signaling was enhanced and cytoskeletal actin was activated in iPSCs cultured on iMatrix-511. In conclusion, laminin-511 strongly activated the cell survival by promoting α6β1 integrin-Fyn-RhoA-ROCK signaling in hiPSCs.