Laminin promotes differentiation of rat embryonic stem cells into cardiomyocytes by activating the integrin/FAK/PI3K p85 pathway

Abstract

The generation of germline competent rat embryonic stem cells (rESCs) allows the study of their lineage commitment. Here, we developed a highly efficient system for rESC‐derived cardiomyocytes, and even the formation of three‐dimensional (3D)‐like cell clusters with cTNT and α‐Actinin. We have validated that laminin can interact with membrane integrin to promote the phosphorylation of both phosphatidylinositol 3‐kinase (PI3K) p85 and the focal adhesion kinase (FAK). In parallel, GATA4 was up‐regulated. Upon inhibiting the integrin, laminin loses the effect on cardiomyocyte differentiation, accompanied with a down‐regulation of phosphorylation level of PI3K p85 and FAK. Meanwhile, the expression of Gata4 was inhibited as well. Taken together, laminin is a crucial component in the differentiation of rESCs into cardiomyocytes through increasing their proliferation via interacting with integrin pathway. These results provide new insights into the pathways mediated by extracellular laminin involved in the fate of rESC‐derived cardiomyocytes.

Cues from human atrial extracellular matrix enrich the atrial differentiation of human induced pluripotent stem cell-derived cardiomyocytes

“…Classically, single purified ECM proteins have been used in in vitro studies 43,44 to describe their ability to induce cellular responses. However, reproducing the molecular complexity and heterogeneity of cardiac ECM may increase the relevance of in vitro studies.…”

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

“…Interestingly, although the inhibition of FAK expression blocks VCAM-1, it does not affect NF-κB activation [10,65]. In this process, the activation of MAPKs does not affect VCAM-1 expression and FAK inhibition can promote the expression of GATA4 transcription factors [98]. This is mediated by the function of the nuclear FAK scaffold that interacts with GATA4 and the ubiquitin protein E3 ligase chips.…”

Agrin-Mediated Cardiac Regeneration: Some Open Questions

“…Together with the evidence that mutations or complete lack of laminin 211 are known to cause severe forms of congenital muscular dystrophy (CMD), these results stress the important role of laminin for adult skeletal muscle stabilization (Yurchenco et al, 2018) and cardiac muscle stability (Nguyen et al, 2019). Other laminins too (including laminin 511, 521, and 221) are known to play an important role for the differentiation of stem cells into cardiomyocytes (Wang et al, 2019;Yap et al, 2019;Chanthra et al, 2020). Recent evidence from studies in Drosophila suggests the possible involvement of β-DG in the Hippo signaling pathway as a mechano-receptor within muscle cells (Yatsenko et al, 2020), thus it is worth noting that the DG-Hippo pathway axis might have an evolutionarily conserved role in mediating muscle growth and regeneration.…”