Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis.

Unlabelled: The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease.

Pulmonary Fibrosis Ferret Model Demonstrates Sustained Fibrosis, Restrictive Physiology, and Aberrant Repair.

Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans.

Action potential conduction in the mouse and rat vagus nerve is dependent on multiple voltage-gated sodium channels (Na1s).

Action potential (AP) conduction depends on voltage-gated sodium channels, of which there are nine subtypes. The vagus nerve, comprising sensory afferent fibers and efferent parasympathetic fibers, provides autonomic regulation of visceral organs, but the voltage-gated sodium channels (Na1) subtypes involved in its AP conduction are poorly defined. We studied the A- and C-waves of electrically stimulated compound action potentials (CAPs) of the mouse and rat vagus nerves with and without Na1 inhibitor administration: tetrodotoxin (TTX), PF-05089771 (mouse Na1.

Role of Na 1.7 in action potential conduction along human bronchial vagal afferent C-fibres.

Background And Purpose: The purpose of this study was to determine the role of Na 1.7 in action potential conduction in C-fibres in the bronchial branches of the human vagus nerve.

Experimental Approach: Bronchial branches of the vagus nerve were dissected from human donor tissue.

Contribution of tetrodotoxin-sensitive, voltage-gated sodium channels (Na1) to action potential discharge from mouse esophageal tension mechanoreceptors.

Action potentials depend on voltage-gated sodium channels (Na1s), which have nine α subtypes. Na1 inhibition is a target for pathologies involving excitable cells such as pain. However, because Na1 subtypes are widely expressed, inhibitors may inhibit regulatory sensory systems.