2. Academic Validation
  3. The T-type voltage-gated Ca2+ channel CaV3.1 involves in the disruption of respiratory epithelial barrier induced by Pasteurella multocida toxin

The T-type voltage-gated Ca2+ channel CaV3.1 involves in the disruption of respiratory epithelial barrier induced by Pasteurella multocida toxin

  • Virulence. 2025 Dec;16(1):2466482. doi: 10.1080/21505594.2025.2466482.
Haixin Bi 1 2 3,  Fei Wang 1 2 3,  Lin Lin 1 2 3,  Dajun Zhang 1 2 3,  Menghan Chen 1 2 3,  Yuyao Shang 1 2 3,  Lin Hua 1 2 3,  Huanchun Chen 1 2 3,  Bin Wu 1 2 3,  Zhong Peng 1 2 3
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 2 Hubei Hongshan Laboratory, Wuhan, China.
  • 3 Frontiers Center for Animal Breeding and Sustainable Production, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
PMID: 39950866 DOI: 10.1080/21505594.2025.2466482
Abstract

Pasteurella multocida toxin (PMT) is an exotoxin produced by several members of the zoonotic respiratory pathogen P. multocida. The role of PMT in disrupting the mammalian respiratory barrier remains to be elucidated. In this study, we showed that inoculation of recombinantly expressed PMT increased the permeability of the respiratory epithelial barrier in mouse and respiratory cell models. This was evidenced by a decreased expression of tight junctions (ZO-1, occludin) and adherens junctions (β-catenin, E-cadherin), as well as enhanced cytoskeletal rearrangement. In mechanism, we demonstrated that PMT inoculation induced cytoplasmic CA2+ inflow, leading to an imbalance of cellular CA2+ homoeostasis and endoplasmic reticulum stress. This process further stimulated the RhoA/ROCK signalling, promoting cytoskeletal rearrangement and reducing the expression of tight junctions and adherens junctions. Notably, the T-type voltage-gated CA2+ channel CAV3.1 was found to participate in PMT-induced cytoplasmic CA2+ inflow. Knocking out CAV3.1 significantly reduced the cytotoxicity induced by PMT on swine respiratory epithelial cells and mitigated cytoplasmic CA2+ inflow stimulated by PMT. These findings suggest CAV3.1 contributes to PMT-induced respiratory epithelial barrier disruption.

Keywords

Pasteurella multocida toxin; RhoA/ROCK signalling; T-type voltage-gated Ca2+ channel CaV3.1; endoplasmic reticulum stress; imbalance in cellular Ca2+ homoeostasis; mammalian respiratory epithelial barrier disruption.

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