The role of cell-cell and cell-matrix junctional complexes in sebaceous gland homeostasis and differentiation

Abstract

Sebaceous glands (SG) are essential for maintaining skin integrity, as their lipid-rich secretion (sebum) lubricates and protects the epidermis and hairs. In addition, these glands have an emerging role in immunomodulation and may affect whole-body energy metabolism, besides being an appealing model for research in topics as lipogenesis, stem cell biology and tumorigenesis. In spite of the increasing interest in studying SGs pathophysiology, sebocyte cell-cell and cell-matrix adhesion processes have been only superficially examined, and never in a systematic way. This is regrettable considering the key role of cellular adhesion in general, the specific expression pattern of indivdual junctional complexes, and the reports of structural changes in SGs after altered expression of adhesion-relevant proteins. Here, we review the available information on structural and functional aspects of cell-cell and cell-matrix junctions in sebocytes, and how these processes change under pathological conditions. This information will contribute for better understanding sebocyte differentiation and sebum secretion, and may provide hints for novel therapeutic strategies for skin diseases.

Keywords: Cell–cell adhesion; Cell–matrix adhesion; Junctional complexes; Sebaceous glands; Sebum.

Fig. 1

Structure of of the pilosebaceous unit and cellular architecture of the sebaceous gland. A Schematic drawing of a pilosebaceous unit in sagittal section. B Higher magnification image of the sebaceous gland. The rectangle is enlarged in C to demonstrate the peripheral (SEB-B), differentiation (SEB-1–3) and necrosis (SEB-4) zones

Fig. 2

Overview of cell–cell and cell–matrix adhesion structures

Fig. 3

Comparison of gene expression associated to the gene ontology terms on cell–cell interaction {Tight Junction (GO:0070160), Adherens Junction (GO:0005912), Gap Junction (GO:0005921), Desmosome (GO:0030057)} and cell–matrix interaction {Hemidesmosome (GO:0030056), Focal Adhesion (GO:0005925)}. A Number of adhesion molecules with weak (yellow) or strong (green) expression (legend: below) in mouse (left) and human (right) sebaceous glands according to single-cell transcription studies. This information is retrieved from existing data published together with our previous study [65]. A gene is strong expressed, if its mean expression over all sebaceous gland samples annotated in the original experimental studies [63, 64] is greater or equal compared to the mean expression of any sample. Gene ontology identifier, terms and corresponding gene sets have been annotated within our previous study [65]. B Difference in base-10 logarithmic mean gene expression for matched-pair lesion and non-lesion samples [66]: Atopic dermatitis (left, 4 patients) and psoriasis (right, 3 patients). Each dot represents one gen from one matched-pair, thus redundant gene annotation occurs. Genes with a difference in mean expression greater than 1 between lesion (red squares) and non-lesion (blue triangles) are highlighted (legend: below) for atopic dermatitis and psoriasis. For psoriasis no non-lesion sample with this difference occurs

Fig. 4

Summary of the localisation of cell–cell adhesion structures in sebocytes at the different zones. SEB: Sebocytes, BM: Basal membrane, TJ: Tight junction, AJ: Adherens junction, DSM: Desmosome, GJ: Gap junction