Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis

Neidhart, Berna; Kowalska, Malwina; Valentin, Jules D. P.; Gall, Flavio; Ren, Qun; Riedl, Rainer; Pot, Simon; Rottmar, Markus

doi:10.1021/acs.biomac.0c01473

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis
Authors:	Neidhart, Berna Kowalska, Malwina Valentin, Jules D. P. Gall, Flavio Ren, Qun Riedl, Rainer Pot, Simon Rottmar, Markus
et. al:	No
DOI:	10.1021/acs.biomac.0c01473
Published in:	Biomacromolecules
Volume(Issue):	22
Issue:	2
Page(s):	629
Pages to:	639
Issue Date:	2021
Publisher / Ed. Institution:	American Chemical Society
ISSN:	1525-7797 1526-4602
Language:	English
Subjects:	Immunology; Infectious disease; Peptidomimetics; Peptides and proteins; Differentiation
Subject (DDC):	540: Chemistry
Abstract:	Matrix metalloproteinase 9 (MMP-9) has a key role in many biological processes, and while it is crucial for a normal immune response, excessive release of this enzyme can lead to severe tissue damage, as evidenced by proteolytic digestion and perforation of the cornea during infectious keratitis. Current medical management strategies for keratitis mostly focus on antibacterial effects, but largely neglect the role of excess MMP activity. Here, a cyclic tissue inhibitor of metalloproteinase (TIMP) peptidomimetic, which downregulated MMP-9 expression both at the mRNA and protein levels as well as MMP-9 activity in THP-1-derived macrophages, is reported. A similar downregulating effect could also be observed on α smooth muscle actin (α-SMA) expression in fibroblasts. Furthermore, the TIMP peptidomimetic reduced Pseudomonas aeruginosa-induced MMP-9 activity in an ex vivo porcine infectious keratitis model and histological examinations demonstrated that a decrease of corneal thickness, associated with keratitis progression, was inhibited upon peptidomimetic treatment. The presented approach to reduce MMP-9 activity thus holds great potential to decrease corneal tissue damage and improve the clinical success of current treatment strategies for infectious keratitis.
URI:	https://www.dora.lib4ri.ch/empa/islandora/object/empa:24355 https://digitalcollection.zhaw.ch/handle/11475/21814
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Published as part of the ZHAW project:	Burn Wound Treatment
Appears in collections:	Publikationen Life Sciences und Facility Management

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Neidhart, B., Kowalska, M., Valentin, J. D. P., Gall, F., Ren, Q., Riedl, R., Pot, S., & Rottmar, M. (2021). Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis. Biomacromolecules, 22(2), 629–639. https://doi.org/10.1021/acs.biomac.0c01473

Neidhart, B. et al. (2021) ‘Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis’, Biomacromolecules, 22(2), pp. 629–639. Available at: https://doi.org/10.1021/acs.biomac.0c01473.

B. Neidhart et al., “Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis,” Biomacromolecules, vol. 22, no. 2, pp. 629–639, 2021, doi: 10.1021/acs.biomac.0c01473.

NEIDHART, Berna, Malwina KOWALSKA, Jules D. P. VALENTIN, Flavio GALL, Qun REN, Rainer RIEDL, Simon POT und Markus ROTTMAR, 2021. Tissue inhibitor of metalloproteinase (TIMP) peptidomimetic as an adjunctive therapy for infectious keratitis. Biomacromolecules [online]. 2021. Bd. 22, Nr. 2, S. 629–639. DOI 10.1021/acs.biomac.0c01473. Verfügbar unter: https://www.dora.lib4ri.ch/empa/islandora/object/empa:24355

Neidhart, Berna, Malwina Kowalska, Jules D. P. Valentin, Flavio Gall, Qun Ren, Rainer Riedl, Simon Pot, and Markus Rottmar. 2021. “Tissue Inhibitor of Metalloproteinase (TIMP) Peptidomimetic as an Adjunctive Therapy for Infectious Keratitis.” Biomacromolecules 22 (2): 629–39. https://doi.org/10.1021/acs.biomac.0c01473.

Neidhart, Berna, et al. “Tissue Inhibitor of Metalloproteinase (TIMP) Peptidomimetic as an Adjunctive Therapy for Infectious Keratitis.” Biomacromolecules, vol. 22, no. 2, 2021, pp. 629–39, https://doi.org/10.1021/acs.biomac.0c01473.