The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity

• DOI: 10.3389/fcell.2021.625719
• Publication Date: 2021-05-03T05:06:36Z
• Authors: Sandra Chánez-Par...; Armando Montoya-G...; Karla F. Castro-O...; Julio García-Cordero; Leticia Cedillo-B...; Mineko Shibayama; Porfirio Nava; Sven Flemming; Nicolas Schlegel; Alexis M. Gautreau; Hilda Vargas-Robles; Ricardo Mondragón...; Michael Schnoor
• Keywords: Adherens junction; Occludin

The intestinal epithelial barrier (IEB) depends on stable interepithelial protein complexes such as tight junctions (TJ), adherens (AJ), and the actin cytoskeleton. During inflammation, IEB is compromised due to TJ internalization remodeling. An important regulator actin-related 2/3 (Arp2/3) complex, which induces branching. Activation of Arp2/3 by nucleation-promoting factors required for formation monolayers, but little known about relevance inhibition endogenous inhibitory proteins regulation. We found that recently identified arpin was strongly expressed in cells. Arpin expression decreased response tumor necrosis factor (TNF)α interferon (IFN)γ treatment, whereas gadkin interacting with C-kinase α-subunit 1 (PICK1), other inhibitors, remained unchanged. Of note, coprecipitated occludin claudin-1 AJ E-cadherin. depletion altered architecture both TJ, increased filament content actomyosin contractility, significantly permeability, demonstrating indeed maintaining integrity. experimental colitis mice, also decreased. Analyzing colon tissues from ulcerative patients Western blot, we different levels overall no significant changes. However, acutely inflamed areas, reduced compared non-inflamed areas. Importantly, receiving mesalazine had higher than untreated patients. As (theoretically meaning more active Arp2/3) wanted know whether would show opposite. Indeed, specific inhibitor CK666 ameliorated TNFα/IFNγ-induced permeability established Caco-2 monolayers preventing disruption. treatment attenuated development, tissue damage, disruption, dextran sulphate sodium (DSS)-treated mice. Our results demonstrate loss triggers dysfunction during inflammation low can be considered a novel hallmark acute inflammation.