CRISPR-Based Activation of Endogenous Expression of TPM1 Inhibits Inflammatory Response of Primary Human Coronary Artery Endothelial and Smooth Muscle Cells Induced by Recombinant Human Tumor Necrosis Factor α

• DOI: 10.3389/fcell.2021.668032
• Publication Date: 2021-09-17T05:55:44Z
• Authors: Maciej Gagat; Wioletta Zielińska; Klaudia Mikołajczyk; Jan Zabrzyński; Adrian Krajewski; Anna Klimaszewska...; Dariusz Grzanka; Alina Grzanka
• Keywords: Proinflammatory cytokine

Tumor necrosis factor α (TNFα) is one of the most important proinflammatory cytokines, which affects many processes associated with growth and characteristics endothelial, smooth muscle, immune system cells. However, there no correlation between in vivo vitro studies on its role endothelial cell proliferation migration. In this study, we examined effect recombinant human (rh) TNFα produced HEK293 cells primary coronary artery (pHCAECs) context F-actin organization such as migration adhesion. Furthermore, evaluated possibility inhibition inflammatory response by CRISPR-based regulation TPM1 gene expression. We showed that TNFα-induced activation pHCAECs was related to reorganization actin cytoskeleton into parallel-arranged stress fibers running along longer axis pHCAECs. It allowed for directed parallel motion during coordinated This change promoted strong but discontinuous cell–cell contacts involved signalization migrating Moreover, form intercellular connections together locally increased adhesion formation migrasomes further migracytosis. Stabilization through endogenous expression resulted following treatment rh stabilization junctions reduced cleavage vascular cadherin (VE-cadherin) maintenance stable levels α- β-catenins. also activation, proliferation, muscle Therefore, products may be a potential therapeutic target disorders.