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. 2024 Feb 2;13(3):278. doi: 10.3390/cells13030278

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© 2024 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Suppression of AKT signaling in FLNC^KO iPSC-CMs. (A) Enrichment of PI3K-AKT signaling pathway, MAPK signaling (p = 3.09 × 10⁻⁸⁰) pathway, and actin cytoskeleton DEGs in FLNC^KO compared to isogenic control iPSC-CMs. (B) The molecular interaction network analysis revealed PIK3 kinase regulatory subunit 1 (PI3KR1) to be the core molecule. (C) Immunoblots showed decreased p-AKT expression levels in FLNC^KO iPSC-CMs compared to isogenic control iPSC-CMs; total AKT expression levels were also significantly increased compared to isogenic control iPSC-CMs. (D) Quantitative representation of immunoblots in C. (E) PHLPP1 mRNA was increased in FLNC^KO compared to healthy hiPSC-CMs, and treatment with crenolanib significantly downregulates PHLPP1 mRNA levels. All experiments were independently repeated three times.