Biological Effects of SLURP-1 on Human Keratinocytes
Open accessAbstract
A novel paradigm of keratinocyte (KC) regulation via nicotinic acetylcholine receptors (nAChR) has been discovered in studies of SLURP (secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein)-1 in Mal de Meleda. We cloned human SLURP-1 and produced recombinant protein and the monoclonal antibody 336H12-1A3 that visualized native SLURP-1. SLURP-1 ligated the conventional ligand-binding site of KC nAChR, showing a higher affinity to the [(3)H]nicotine-, compared with the [(3)H]epibatidine-sensitive nAChR. SLURP-1 significantly (p<0.05) increased the activities of caspases 3 and 8, and the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling-positive cells. The pro-apoptotic activity of SLURP-1 exceeded that of tumor necrosis factor-alpha, suggesting the involvement of separate pathways. In a series of real-time PCR and in-cell western experiments, SLURP-1 significantly (p<0.05) upregulated expression of transglutaminase type I cytokeratin 10, p21, and caspase-3. In the presence of the agonist carbachol, the effects of SLURP-1 on gene expression were augmented, which is in keeping with the notion that SLURP-1 acts as an allosteric agonist at the KC nAChR. Thus, the changes in the cell state induced by SLURP-1 could result from nAChR-mediated effects on the KC gene expression. These results suggest that the biological role of SLURP-1 in the epidermis is to provide fine tuning of the physiologic regulation of KC functions through the cholinergic pathways.
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SLURPs enhance nicotine-stimulated proliferation of lymphocytes and keratinocytes as well as oral and lung cancer cell proliferation.
“SLURPs enhance this process (123) as well as oral and lung cancer cell proliferation (124).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [123]
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Self-citation
- Authors
- Arredondo, J., Chernyavsky, A. I., Webber, R. J., & Grando, S. A.
- Affiliations
- University of California, Davis (US)
- Research & Diagnostic Antibodies (United States) (US)
- Corresponding author
- Grando, Sergei A.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 125
- Issue
- 6
- Pages
- 1236-1241
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1990264320
- Cited by
- 154
- References
- 31
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 12
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM062136, GM 62136)
- National Institute of Dental and Craniofacial Research (R01DE014173, DE14173)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- SLURP-1, keratinocytes, nicotinic acetylcholine receptors, Mal de Meleda, apoptosis, caspase-3, caspase-8, cytokeratin 10, p21, carbachol, allosteric agonists, cholinergic neurotransmission, epidermis, gene expression regulation
- MeSH terms
- Antigens, Ly, Cell Division, Cells, Cultured, Epidermis, Humans, Recombinant Proteins, RNA, Urokinase-Type Plasminogen Activator, Keratinocytes, Polymerase Chain Reaction
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