Botulinum Toxin Type A Inhibits Submandibular Secretion via the ERK/miR-124-3p/Specificity Protein 1/Claudin-1 Axis.

Qian-Ying Mao, Yan Huang, Zhuo Chen, Xiao-Feng Shan, Shang Xie, Li-Ling Wu, Ruo-Lan Xiang, Zhi-Gang Cai

Abstract read

In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Qian-Ying MaoNational Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, No. 22 Zhong Guan Cun South Street, Haidian District, Beijing 100081, China.

Yan HuangXiamen Key Laboratory of Stomotalogical Disease Diagnosis and Treatment, Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Xiamen Medical College, Xiamen 361102, China.ORCID 0000-0002-0126-7810

Zhuo ChenKey Laboratory of Molecular Cardiovascular Sciences, Department of Physiology and Pathophysiology, Ministry of Education, Peking University School of Basic Medical Sciences, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Xiao-Feng ShanNational Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, No. 22 Zhong Guan Cun South Street, Haidian District, Beijing 100081, China.

Shang XieNational Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, No. 22 Zhong Guan Cun South Street, Haidian District, Beijing 100081, China.ORCID 0000-0003-1461-695X

Li-Ling WuKey Laboratory of Molecular Cardiovascular Sciences, Department of Physiology and Pathophysiology, Ministry of Education, Peking University School of Basic Medical Sciences, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Ruo-Lan XiangKey Laboratory of Molecular Cardiovascular Sciences, Department of Physiology and Pathophysiology, Ministry of Education, Peking University School of Basic Medical Sciences, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Zhi-Gang CaiNational Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, No. 22 Zhong Guan Cun South Street, Haidian District, Beijing 100081, China.

Funding

National Natural Science Foundation of China 82071133

6 · The paper itself

Abstract

Botulinum toxin type A (BTXA) is widely used for the treatment of sialorrhea; however, its mechanism remains unclear. Tight junctions (TJs) are limiting factors for salivary secretion through the paracellular pathway in the salivary gland, among which claudin-1 (Cldn1) is a TJ protein that mainly plays a barrier role. This study observed that Cldn1 was upregulated in BTXA-treated rats' submandibular glands and SMG-C6 cells. Knockdown of Cldn1 reversed the BTXA-induced reduction in paracellular permeability. The transcription factor specificity protein-1 (Sp1), which binds to the Cldn1 promoter, was also upregulated by BTXA, and its expression was linked to the ERK1/2 pathway. Inhibition of ERK1/2 by U0126 reversed the BTXA-induced upregulation of Sp1 and Cldn1, as well as the reduction in paracellular permeability. MiR-124-3p, which directly targets Sp1, was downregulated by BTXA, but its overexpression counteracted Sp1 and Cldn1 upregulation. Although miR-124-3p did not affect ERK1/2 phosphorylation, ERK1/2 inhibition reversed the BTXA-induced decrease in miR-124-3p expression. These findings reveal a regulatory pathway through which BTXA reduces paracellular permeability in SMG-C6 cells via the ERK1/2/miR-124-3p/Sp1/Cldn1 axis.

Indexed as

Botulinum Toxins, Type AClaudin-1MAP Kinase Signaling SystemMicroRNAsSp1 Transcription FactorSubmandibular GlandAnimalsMaleRatsRats, Sprague-DawleyBotulinum Toxins, Type AClaudin-1Cldn1 protein, ratMicroRNAsSp1 Transcription Factorbotulinum toxin type AmiR-124-3pspecific protein 1submandibular glandtight junction

Identifiers

PMID40940777

DOI10.3390/cells14171366

PMCPMC12428761

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.