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Spatiotemporal expression, distribution, and processing of POMC and POMC-derived peptides in murine skin
J E Mazurkiewicz1, D Corliss, A Slominski
1Department of Microbiology, Immunology and Molecular Genetics, Albany Medical College, Albany, New York 12208, USA.
Abstract:
In murine skin, after depilation-induced anagen, there was a differential spatial and temporal expression of pro-opiomelanocortin (POMC) mRNA, of the POMC-derived peptides beta-endorphin, ACTH, beta-MSH, and alpha-MSH, and of the prohormone convertases PC1 and PC2 in epidermal and hair follicle keratinocytes and in the cells of sebaceous units. Using a combination of in situ hybridization histochemistry and immunohistochemistry, we found cell-specific variations in the expression of POMC mRNA that were consistent with immunoreactivities for POMC-derived peptides. Cells that contained POMC peptide immunoreactivity (IR) also expressed POMC mRNA, and where the IR increased there was a parallel increase in mRNA. The levels of PC1-IR and PC2-IR also showed cell-specific variations and were present in the same cells that contained the POMC peptides. Based on the cleavage specificities of these convertases and on the spatial and temporal expression of the convertases and of ACTH, beta-endorphin, beta-MSH, and alpha-MSH, we can infer that the activities of PC1 and PC2 are responsible for the cell-specific differential processing of POMC in murine skin.
Insights
Murine skin keratinocytes express pro-opiomelanocortin (POMC) mRNA and peptides, regulated by convertases PC1 and PC2. This study reveals cell-specific POMC processing during hair follicle cycling.
Area of Science:
- Dermatology
- Molecular Biology
- Endocrinology
Background:
- Pro-opiomelanocortin (POMC) is a precursor to various peptides with diverse functions.
- The role and processing of POMC in skin, particularly within hair follicles and sebaceous units, remain incompletely understood.
Purpose of the Study:
- To investigate the spatial and temporal expression of POMC mRNA and its derived peptides in murine skin during the hair follicle cycle.
- To determine the involvement of prohormone convertases (PC1 and PC2) in the cell-specific processing of POMC in skin keratinocytes.
Main Methods:
- In situ hybridization histochemistry to detect POMC mRNA.
- Immunohistochemistry to identify POMC-derived peptides (beta-endorphin, ACTH, beta-MSH, alpha-MSH) and convertases (PC1, PC2).
- Analysis of expression patterns in epidermal keratinocytes, hair follicle keratinocytes, and sebaceous unit cells after depilation-induced anagen.
Main Results:
- Differential spatial and temporal expression of POMC mRNA and peptides was observed in skin cells.
- POMC peptide immunoreactivity correlated directly with POMC mRNA levels.
- PC1 and PC2 immunoreactivity were found in the same cells expressing POMC peptides, indicating their role in POMC processing.
Conclusions:
- Murine skin keratinocytes and sebaceous cells express POMC and its processing enzymes.
- PC1 and PC2 activities are responsible for cell-specific differential processing of POMC in the skin.
- These findings highlight a novel role for POMC peptides and their processing in skin biology and hair follicle dynamics.