Life or death by NFκB, Losartan promotes survival in dy2J/dy2J mouse of MDC1A

Cell Death & Disease
M ElbazY Nevo

Abstract

Inflammation and fibrosis are well-defined mechanisms involved in the pathogenesis of the incurable Laminin α2-deficient congenital muscular dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous study showed treatment with Losartan, an angiotensin II type I receptor antagonist, improved muscle strength and reduced fibrosis through transforming growth factor beta (TGF-β) and mitogen-activated protein kinases (MAPK) signaling inhibition in the dy(2J)/dy(2J) mouse model of MDC1A. Here we show for the first time that Losartan treatment up-regulates and shifts the nuclear factor kappa B (NFκB) signaling pathway to favor survival versus apoptosis/damage in this animal model. Losartan treatment was associated with significantly increased serum tumor necrosis factor alpha (TNF-α) level, p65 nuclei accumulation, and decreased muscle IκB-β protein level, indicating NFκB activation. Moreover, NFκB anti-apoptotic target genes TNF receptor-associated factor 1 (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following Losartan treatment. Losartan induced protein expression toward a pro-survival profile as BCL-2 expression levels...Continue Reading

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Citations

Mar 8, 2016·Neuromuscular Disorders : NMD·M SaunierUNKNOWN CMD Animal Model Consortium
Sep 28, 2016·Seminars in Cell & Developmental Biology·Antonio L Serrano, Pura Muñoz-Cánoves
Sep 22, 2019·International Journal of Molecular Sciences·Jaione Lasa-ElgarrestaAinara Vallejo-Illarramendi
May 28, 2020·Frontiers in Molecular Neuroscience·Kinga I Gawlik, Madeleine Durbeej
Oct 23, 2020·Journal of Cellular Physiology·Ya GaoJianghui Dong

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Methods Mentioned

BETA
biopsies
PCR
transgenic

Software Mentioned

BD CBA Software
chemi DOC XRS + image lab

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