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Editorial
. 2022 Nov 12:2:100019.
doi: 10.1016/j.jmccpl.2022.100019. eCollection 2022 Dec.

ITCH puts the brakes on septic cardiomyopathy

Dominic P Del Re  1 , Qinghang Liu  2
Affiliations
Editorial

ITCH puts the brakes on septic cardiomyopathy

Dominic P Del Re et al. J Mol Cell Cardiol Plus. .
No abstract available

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Figures

Fig. 1
Fig. 1
ITCH attenuates septic cardiomyopathy by inhibiting NFκB signaling. Upon LPS stimulation, TLR4 recruits MyD88, IRAKs, and TRAF6 to assemble a signaling complex, where TRAF6 undergoes K63-linked auto-ubiquitination to recruit and activate downstream kinases TAK1 and IKKs. This process requires the TAK1 regulatory subunit TAB2 (or TAB3) and IKK regulatory subunit NEMO, both of which have ubiquitin-binding functions. Activation of this complex results in phosphorylation of IκB and subsequent activation of NFκB, which promotes the production of inflammatory cytokines, leading to septic cardiomyopathy. ITCH negatively regulates NFκB signaling by targeting TRAF6 and TAK1, possibly in coordination with A20 or CYLD. Myocardial ITCH is downregulated in sepsis though an undefined mechanism, which contributes to an enhanced inflammatory response and septic cardiomyopathy. Created with BioRender.
See this image and copyright information in PMC

Comment on

  • doi: 10.1016/j.jmccpl.2022.100018

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