{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:42:23Z","timestamp":1760060543730,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071133"],"award-info":[{"award-number":["82071133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2019 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.<\/jats:p>","DOI":"10.3390\/cells14171366","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T12:04:28Z","timestamp":1756814668000},"page":"1366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Botulinum Toxin Type A Inhibits Submandibular Secretion via the ERK\/miR-124-3p\/Specificity Protein 1\/Claudin-1 Axis"],"prefix":"10.3390","volume":"14","author":[{"given":"Qian-Ying","family":"Mao","sequence":"first","affiliation":[{"name":"National 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-7810","authenticated-orcid":false,"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiamen Key Laboratory of Stomotalogical Disease Diagnosis and Treatment, Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Xiamen Medical College, Xiamen 361102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Key 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Feng","family":"Shan","sequence":"additional","affiliation":[{"name":"National 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-695X","authenticated-orcid":false,"given":"Shang","family":"Xie","sequence":"additional","affiliation":[{"name":"National 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"Key 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruo-Lan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Key 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Gang","family":"Cai","sequence":"additional","affiliation":[{"name":"National 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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Isaacson, J., Patel, S., Torres-Yaghi, Y., and Pagan, F. 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