Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing

Wittner L, Wagener L, Wiese JJ, Stolzer I, Krug SM, Naschberger E, Jackstadt R, Beyaert R, Atreya R, Kühl AA, Sturm G, Gonzalez-Acera M, Patankar J, Becker C, Siegmund B, Trajanoski Z, Winner B, Neurath M, Schumann M, Günther C (2023)

Publication Language: English

Publication Type: Journal article

Publication year: 2023

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 24

Article Number: 7402

Journal Issue: 8

DOI: 10.3390/ijms24087402

Abstract

The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases.

Authors with CRIS profile

Leonie Wittner Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Iris Stolzer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Elisabeth Naschberger Medizinische Fakultät Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie Beate Winner Medizinische Fakultät Markus Neurath Lehrstuhl für Innere Medizin I Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Universiteit Gent (UGent) / Ghent University BE Belgium (BE) Medizinische Universität Innsbruck AT Austria (AT) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE)

How to cite

APA:

Wittner, L., Wagener, L., Wiese, J.J., Stolzer, I., Krug, S.M., Naschberger, E.,... Günther, C. (2023). Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing. International Journal of Molecular Sciences, 24(8). https://dx.doi.org/10.3390/ijms24087402

MLA:

Wittner, Leonie, et al. "Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing." International Journal of Molecular Sciences 24.8 (2023).

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