Proteome analysis of human sebaceous follicle infundibula extracted from healthy and acne-affected skin

Abstract

Acne vulgaris is a very common disease of the pilosebaceous unit of the human skin. The pathological processes of acne are not fully understood. To gain further insight sebaceous follicular casts were extracted from 18 healthy and 20 acne-affected individuals by cyanoacrylate-gel biopsies and further processed for mass spectrometry analysis, aiming at a proteomic analysis of the sebaceous follicular casts. Human as well as bacterial proteins were identified. Human proteins enriched in acne and normal samples were detected, respectively. Normal follicular casts are enriched in proteins such as prohibitins and peroxiredoxins which are involved in the protection from various stresses, including reactive oxygen species. By contrast, follicular casts extracted from acne-affected skin contained proteins involved in inflammation, wound healing and tissue remodeling. Among the most distinguishing proteins were myeloperoxidase, lactotransferrin, neutrophil elastase inhibitor and surprisingly, vimentin. The most significant biological process among all acne-enriched proteins was 'response to a bacterium'. Identified bacterial proteins were exclusively from Propionibacterium acnes. The most abundant P. acnes proteins were surface-exposed dermatan sulphate adhesins, CAMP factors, and a so far uncharacterized lipase in follicular casts extracted from normal as well as acne-affected skin. This is a first proteomic study that identified human proteins together with proteins of the skin microbiota in sebaceous follicular casts.

Figure 1. Experimental pipeline of processing extracted human follicular cast material for mass spectrometry analysis.

Figure 2. Interaction analysis of human proteins enriched in follicular casts extracted from acne-affected skin sites.

The human proteins that are enriched in acne-affected samples (acne-A1) compared to unaffected nasal follicular casts (nose-A1) were analyzed for known protein-protein interactions with the STRING program. The analysis highlighted a cluster of proteins involved in inflammation and host response to a bacterial impact (in yellow) and a cluster of actin-related functions involved in tissue remodeling and repair (in red). A small cluster (in blue) comprises mainly proteins of the 14-3-3 protein family which mediates signal transduction. The complete list of enriched proteins can be found in Tables S2C; a selection is listed in Table 2.