Skin proteomics – analysis of the extracellular matrix in health and disease

ABSTRACT

Introduction

The skin protects the human body from external insults and regulates water and temperature homeostasis. A highly developed extracellular matrix (ECM) supports the skin and instructs its cell functions. Reduced functionality of the ECM is often associated with skin diseases that cause physical impairment and also have implications on social interactions and quality of life of affected individuals.

Areas covered

With a focus on the skin ECM we discuss how mass spectrometry (MS)-based proteomic approaches first contributed to establishing skin protein inventories and then facilitated elucidation of molecular functions and disease mechanisms.

Expert opinion

MS-based proteomic approaches have significantly contributed to our understanding of skin pathophysiology, but also revealed the challenges in assessing the skin ECM. The numerous posttranslational modifications of ECM proteins, like glycosylation, crosslinking, oxidation, and proteolytic maturation in disease settings can be difficult to tackle and remain understudied. Increased ease of handling of LC-MS/MS systems and automated/streamlined data analysis pipelines together with the accompanying increased usage of LC-MS/MS approaches will ensure that in the coming years MS-based proteomic approaches will continue to play a vital part in skin disease research. They will facilitate the elucidation of molecular disease mechanisms and, ultimately, identification of new druggable targets.

KEYWORDS:

• Skin fragility; wound healing; mass spectrometry

Article highlights

• Skin functions are dependent on a highly complex extracellular matrix (ECM).

• Both keratinocytes and skin fibroblasts contribute to the ECM.

• MS-based proteomic approaches yield unprecedented insights into the composition and regulation of the proteome of skin and skin cells.

• MS-based proteomic analyses of PTM and crosslinked ECM proteins are challenging and require special protocols

• Current robust MS-based proteomic analyses help identify new druggable targets in skin diseases.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Swiss National Science Foundation (SNSF) and the canton of Fribourg (JD), the German Research Foundation (DFG) through DE 1757/3-2 (JD), NY90/2-1, NY90/3-2, NY90/5-1 and SFB850 project B11 (AN), and a research grant from the dystrophic epidermolysis bullosa research association (DEBRA) Nyström-Bruckner-Tuderman 1 (LBT, AN).