Intracellular signaling pathways involved in the regulation of gene expression by pilocarpine.

Autor: Sakazume H; Course of Clinical Science, Field of Oral and Maxillofacial Surgery and Systemic Medicine, Oral and Maxillofacial Surgery, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Japan., Morita T; Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University, Japan. Electronic address: moritat@ngt.ndu.ac.jp., Yamaguchi H; Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University, Japan., Tanaka A; Course of Clinical Science, Field of Oral and Maxillofacial Surgery and Systemic Medicine, Oral and Maxillofacial Surgery, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Japan; Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Niigata, The Nippon Dental University, Japan.
Jazyk: angličtina
Zdroj: Journal of oral biosciences [J Oral Biosci] 2024 Dec; Vol. 66 (4), pp. 81-87. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1016/j.job.2024.07.004
Abstrakt: Objectives: Pilocarpine is commonly used clinically to treat dry mouth. The long-term administration of pilocarpine reportedly improves salivary secretion more effectively than short-term administration. Therefore, we hypothesized that pilocarpine alters gene expression in salivary glands via muscarinic receptor stimulation. This study aimed to investigate the effects of pilocarpine use on gene expression mediated by mitogen-activated protein kinase (MAPK) activity.
Methods: The effects of pilocarpine on gene expression were investigated in rats and human salivary gland (HSY) cells using several inhibitors of intracellular signaling pathways. Gene expression in the rat submandibular gland and HSY cells was determined using reverse transcription-quantitative polymerase chain reaction analysis of total RNA.
Results: In animal experiments, at 7 days after pilocarpine stimulation, Ctgf and Sgk1 expressions were increased in the submandibular gland. In cell culture experiments, pilocarpine increased Ctgf expression in HSY cells. The mitogen-activated protein kinase kinase inhibitor trametinib, the Src inhibitor PP2, and the muscarinic acetylcholine receptor antagonist atropine suppressed the effect of pilocarpine on gene expression.
Conclusions: Pilocarpine enhances Ctgf and Sgk1 expressions by activating Src-mediated MAPK activity. Although further studies are required to fully understand the roles of Ctgf and Sgk1, changes in gene expression may play an important role in improving salivary secretions.
Competing Interests: Conflicts of Interest The authors declare no conflict of interest.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE