Alpha- and beta-melanocyte stimulating hormone positively impact lipogenesis of meibomian gland cells in vitro and ex vivo - 20/03/25
, Eileen Socher a, Antonio Bergua b, Thilo Schikorra a, Benedikt Kleinsasser a, Fabian Garreis a, Martin Schicht a, Jana Dietrich a, Friedrich Paulsen aAbstract |
Purpose |
The meibomian glands produce a lipid-rich secretion that forms the superficial layer of the tear film, preventing excessive evaporation. Dysfunction of these glands (MGD) is the primary cause of dry eye disease (DED), a growing public health concern. Currently, there are limited pharmacological treatments for DED. However, α-/β-melanocyte-stimulating hormones (α-/β-MSH), ligands of the melanocortin receptors (MCR), are known to regulate lipogenesis and differentiation in sebaceous glands. This study investigated the influence of α-/β-MSH on exocrine secretion in human meibomian glands.
Methods |
Immunohistochemistry and RT-PCR for MCR expression were performed in human meibomian glands and an immortalized human meibomian gland epithelial cell line (ihMGECs). The effects of α-/β-MSH (agonists) and JNJ-10229570 (antagonist) in ihMGECs on lipid production and MCR response were analyzed using Oil-Red-O staining, transmission electron microscopy, qPCR, and a cAMP assay. Additionally, the effect of α-/β-MSH on an ex vivo organotypic slice culture (OSC) of human eyelids was investigated.
Results |
MCR expression was confirmed in human meibomian glands. Stimulation with α-/β-MSH increased cAMP levels and MCR expression. α-/β-MSH dose-dependently induced lipid production in ihMGECs and OSC, resulting in increased lipid droplet formation and upregulation of lipogenesis markers. Co-administration of JNJ-10229570 suppressed this effect.
Conclusion |
Our data show for the first time that human meibomian glands express MCRs and that stimulation/inhibition of MCRs alters cAMP response, MCR expression, and lipogenesis markers, thereby affecting the genesis of meibum. Therefore, α-/β-MSH positively impacts meibum production and should be considered in the context of changes in glandular secretion in MGD and potential treatments.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Melanocortin receptors are expressed in human meibomian glands. |
• | α-/β-MSH induce intracellular cAMP and melanocortin receptor expression. |
• | α-/β-MSH upregulate lipogenesis markers and lipid droplet production. |
Abbreviations : α-MSH, β-MSH, ACTH, BPE, DED, FABP4, IhMGEC, MCR, Md, MNE, MGD, ORO, OSC, PPARγ, POMC, SCD
Keywords : Dry eye disease, Meibomian gland, Meibomian gland dysfunction, Melanocortin receptor, Organotypic slice culture, α-MSH, β-MSH
Plan
Vol 185
Article 117937- avril 2025 Retour au numéro
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