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Article

Defining the Protease and Protease Inhibitor (P/PI) Proteomes of Healthy and Diseased Human Skin by Modified Systematic Review

by
Callum Stewart-McGuinness
1,†,
Christopher I. Platt
1,*,†,
Matiss Ozols
1,2,3,
Brian Goh
1,
Tamara W. Griffiths
4 and
Michael J. Sherratt
1
1
Division of Cell Matrix Biology & Regenerative Medicine, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester M13 9PT, UK
2
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton CB10 1SA, UK
3
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge CB2 0QQ, UK
4
Centre for Dermatology Research, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9PL, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2022, 12(3), 475; https://doi.org/10.3390/biom12030475
Submission received: 1 February 2022 / Revised: 9 March 2022 / Accepted: 18 March 2022 / Published: 20 March 2022
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease 2.0)

Abstract

Proteases and protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are investigated. Proteomics approaches, such as mass spectrometry, can define proteome signatures (including P/PIs) in tissues; however, they struggle to detect low-abundance proteins. To overcome these issues, we aimed to produce a comprehensive proteome of all P/PIs present in normal and diseased human skin, in vivo, by carrying out a modified systematic review using a list of P/PIs from MEROPS and combining this with key search terms in Web of Science. Resulting articles were manually reviewed against inclusion/exclusion criteria and a dataset constructed. This study identified 111 proteases and 77 protease inhibitors in human skin, comprising the serine, metallo-, cysteine and aspartic acid catalytic families of proteases. P/PIs showing no evidence of catalytic activity or protease inhibition, were designated non-peptidase homologs (NPH), and no reported protease inhibitory activity (NRPIA), respectively. MMP9 and TIMP1 were the most frequently published P/PIs and were reported in normal skin and most skin disease groups. Normal skin and diseased skin showed significant overlap with respect to P/PI profile; however, MMP23 was identified in several skin disease groups, but was absent in normal skin. The catalytic profile of P/PIs in wounds, scars and solar elastosis was distinct from normal skin, suggesting that a different group of P/PIs is responsible for disease progression. In conclusion, this study uses a novel approach to provide a comprehensive inventory of P/PIs in normal and diseased human skin reported in our database. The database may be used to determine either which P/PIs are present in specific diseases or which diseases individual P/PIs may influence.
Keywords: proteome; protease; protease inhibitor; skin; human proteome; protease; protease inhibitor; skin; human

Share and Cite

MDPI and ACS Style

Stewart-McGuinness, C.; Platt, C.I.; Ozols, M.; Goh, B.; Griffiths, T.W.; Sherratt, M.J. Defining the Protease and Protease Inhibitor (P/PI) Proteomes of Healthy and Diseased Human Skin by Modified Systematic Review. Biomolecules 2022, 12, 475. https://doi.org/10.3390/biom12030475

AMA Style

Stewart-McGuinness C, Platt CI, Ozols M, Goh B, Griffiths TW, Sherratt MJ. Defining the Protease and Protease Inhibitor (P/PI) Proteomes of Healthy and Diseased Human Skin by Modified Systematic Review. Biomolecules. 2022; 12(3):475. https://doi.org/10.3390/biom12030475

Chicago/Turabian Style

Stewart-McGuinness, Callum, Christopher I. Platt, Matiss Ozols, Brian Goh, Tamara W. Griffiths, and Michael J. Sherratt. 2022. "Defining the Protease and Protease Inhibitor (P/PI) Proteomes of Healthy and Diseased Human Skin by Modified Systematic Review" Biomolecules 12, no. 3: 475. https://doi.org/10.3390/biom12030475

APA Style

Stewart-McGuinness, C., Platt, C. I., Ozols, M., Goh, B., Griffiths, T. W., & Sherratt, M. J. (2022). Defining the Protease and Protease Inhibitor (P/PI) Proteomes of Healthy and Diseased Human Skin by Modified Systematic Review. Biomolecules, 12(3), 475. https://doi.org/10.3390/biom12030475

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