Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases

Sruthi Vijaya Retnakumar; Ramasatyaveni Geesala; Alexis Bretin; Julien Tourneur-Marsille; Eric Ogier-Denis; Thorsten Maretzky; Hang Thi Thu Nguyen; Sylviane Muller

doi:10.1016/j.jaut.2022.102814

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Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases

Journal article

Open access

Peer reviewed

Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases

Sruthi Vijaya Retnakumar, Ramasatyaveni Geesala, Alexis Bretin, Julien Tourneur-Marsille, Eric Ogier-Denis, Thorsten Maretzky, Hang Thi Thu Nguyen and Sylviane Muller

Journal of autoimmunity, Vol.128, pp.102814-102814

04/2022

DOI: 10.1016/j.jaut.2022.102814

PMID: 35298976

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Abstract

Inflammatory bowel disease (IBD) is a serious public health problem in Western society with a continuing increase in incidence worldwide. Safe, targeted medicines for IBD are not yet available. Autophagy, a vital process implicated in normal cell homeostasis, provides a potential point of entry for the treatment of IBDs, as several autophagy-related genes are associated with IBD risk. We conducted a series of experiments in three distinct mouse models of colitis to test the effectiveness of therapeutic P140, a phosphopeptide that corrects autophagy dysfunctions in other autoimmune and inflammatory diseases. Colitis was experimentally induced in mice by administering dextran sodium sulfate and 2,4,6 trinitrobenzene sulfonic acid. Transgenic mice lacking both il-10 and iRhom2 − involved in tumor necrosis factor α secretion − were also used. In the three models investigated, P140 treatment attenuated the clinical and histological severity of colitis. Post-treatment, altered expression of several macroautophagy and chaperone-mediated autophagy markers, and of pro-inflammatory mediators was corrected. Our results demonstrate that therapeutic intervention with an autophagy modulator improves colitis in animal models. These findings highlight the potential of therapeutic peptide P140 for use in the treatment of IBD. •The risk of developing IBD is associated with polymorphisms in autophagy genes.•We show that autophagy is altered in the colon and spleen of mice with colitis.•The autophagy modulator P140 attenuated clinical disease in experimental colitis.•Defective autophagy was restored after intravenous injection of P140 in mice.•P140, which is safe in autoimmune patients, may be effective for treating IBD.

Autophagy

Colitis

Inflammatory bowel diseases

Murine models

Peptide-based treatment

Details

Title: Subtitle: Targeting the endo-lysosomal autophagy pathway to treat inflammatory bowel diseases
Creators: Sruthi Vijaya Retnakumar - International Drug Development
Ramasatyaveni Geesala - University of Iowa
Alexis Bretin - Microbe, Intestine, Inflammation and Host Susceptibility
Julien Tourneur-Marsille - Centre de Recherche sur l'Inflammation
Eric Ogier-Denis - Oncogenesis Stress Signaling
Thorsten Maretzky - Roy J. and Lucille A. Carver College of Medicine
Hang Thi Thu Nguyen - Microbe, Intestine, Inflammation and Host Susceptibility
Sylviane Muller - International Drug Development
Resource Type: Journal article
Publication Details: Journal of autoimmunity, Vol.128, pp.102814-102814
DOI: 10.1016/j.jaut.2022.102814
PMID: 35298976
NLM abbreviation: J Autoimmun
ISSN: 0896-8411
eISSN: 1095-9157
Publisher: Elsevier Ltd
Language: English
Date published: 04/2022
Academic Unit: Internal Medicine
Record Identifier: 9984359848402771

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