{
  "abstract": "Background and objective\n\nAirway mucus overproduction (predominantly MUC5AC) is a well-recognized pathogenic feature in asthma, but the upstream regulatory mechanisms were enigmatic. Emerging evidence has implied the crucial role for transient receptor potential canonical channel 5 (TRPC5) in the pathogenesis of allergic diseases. Yet, the specific role of TRPC5 in asthma still remains unclear. Thus, this study was aimed to explore the functional role of TRPC5 in toluene diisocyanate (TDI)-induced mixed granulocytic asthma and to delineate the mechanisms by which TRPC5 regulate MUC5AC secretion.Methods\n\nBronchoalveolar lavage fluid (BALF) and mucosal biopsy samples were collected from asthmatic subjects and control. Using a murine model of TDI-induced asthma, we gave the asthmatic mice selective TRPC5 inhibitors ML204, AC1903 or an NLRP3 inhibitor, MCC950. In vitro experiments were performed in a human airway epithelial cell line BEAS-2B.Results\n\nBALF levels of MUC5AC were significantly increased in the recruited asthmatic patients, as well as the levels of HMGB1, and a positive correlation was observed between the two. Expression of TRPC5 was elevated in the airway epithelium of asthmatics when compared to the control. In mice, TDI exposure raised the expression of TRPC5. Blocking TRPC5 with either ML204 or AC1903 dramatically attenuated TDI-induced airway hyperresponsiveness (AHR), airway inflammation and remodeling. Additionally, both antagonists led to inhibited activation of NLRP3 inflammasome and muc5ac secretion in TDI-exposed mice. While pharmacological inhibition of NLRP3 inflammasome suppressed TDI-induced muc5ac secretion. In vitro, TDI induced increased expression of MUC5AC, NLRP3 and TRPC5 in BEAS-2B. Silence of either trpc5 or nlrp3 effectively inhibited MUC5AC hypersecretion in airway epithelium induced by TDI. Besides, TRPC5 agonist (Riluzole) promoted MUC5AC overproduction in airway epithelial cells, which could be suppressed by nlrp3 siRNA.Conclusion\n\nTRPC5 contributes to TDI-induced asthma, and mediates airway epithelial muc5ac hypersecretion by partially activating NLRP3 inflammasome.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pulmonary and Critical Care Medicine, The Second Clinical Medical College, Shenzhen Institute of Respiratory Diseases, Shenzhen Peoples Hospital, Jinan University, The First Affiliated Hospital of SouthernUniversity of Science and Technology, Shenzhen, 518020, China. hxshuyuchen@126.com.",
    "Department of Pulmonary and Critical Care Medicine, The Second Clinical Medical College, Shenzhen Institute of Respiratory Diseases, Shenzhen Peoples Hospital, Jinan University, The First Affiliated Hospital of SouthernUniversity of Science and Technology, Shenzhen, 518020, China.",
    "Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College, Shenzhen Peoples Hospital, Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.",
    "Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Haizhu District, 253 Gongye Middle Avenue, Guangzhou, 510280, China.",
    "Department of Pulmonary and Critical Care Medicine, The Second Clinical Medical College, Shenzhen Institute of Respiratory Diseases, Shenzhen Peoples Hospital, Jinan University, The First Affiliated Hospital of SouthernUniversity of Science and Technology, Shenzhen, 518020, China. wang.lingwei@szhospital.com.",
    "Department of Pulmonary and Critical Care Medicine, The Second Clinical Medical College, Shenzhen Institute of Respiratory Diseases, Shenzhen Peoples Hospital, Jinan University, The First Affiliated Hospital of SouthernUniversity of Science and Technology, Shenzhen, 518020, China. chenrc@vip.163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuyu Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhengqiang He"
    },
    {
      "affs": [
        1
      ],
      "name": "Kai Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuanyuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Li Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Linlin Zheng"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Ma"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhou Cai"
    },
    {
      "affs": [
        1
      ],
      "name": "Shanze Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Lingwei Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Rongchang Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7qtqwd2b4w898.bib",
  "cited_by": 0,
  "doi": "10.1007/s10565-026-10248-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13694367",
  "id": "7qtqwd2b4w898",
  "issns": [
    "0742-2091",
    "1573-6822"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909683",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Asthma and respiratory diseases"
    ]
  ],
  "openalex": "W7171553736",
  "pdf_url": "https://europepmc.org/articles/PMC13694367?pdf=render",
  "pmcid": "PMC13694367",
  "pmid": "42909683",
  "published": "2026-07-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7qtqwd2b4w898.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909683",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909683"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Asthma and respiratory diseases",
      "subfield": "physiology"
    }
  ],
  "title": "TRPC5 mediates MUC5AC secretion via NLRP3 inflammasome in toluene diisocyanate-induced mixed granulocytic asthma.",
  "title_text": "TRPC5 mediates MUC5AC secretion via NLRP3 inflammasome in toluene diisocyanate-induced mixed granulocytic asthma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/7qtqwd2b4w898",
  "venue": "Cell biology and toxicology",
  "versions": []
}