Lung mechanics showing sex‐based differences and circadian time‐of‐day response to bleomycin‐induced lung injury in mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that impairs lung mechanical properties due to dysregulated extracellular matrix remodeling. Lung function assessment is an important physiological endpoint in the mouse model of pulmonary fibrosis (PF) that has gained a broader scientific acceptance in the field. IPF pathophysiology shows sex‐based differences, disproportionately affecting more men compared to women. Prior reports suggest that the circadian clock is perturbed during the pathogenesis of PF. We have comprehensively assessed the sex‐based differences and time‐of‐day response (at Zeitgeber time: ZT0/6:00 a.m. or ZT12/6 p.m.) in lung mechanics among sham (control) versus bleomycin (BLM)‐challenged female and male (C57BL/6: WT) mice using Flexi‐vent. BLM challenge altered lung function significantly in males in both total lung (reduced dynamic compliance, and increased resistance and elastance) as well as lung tissue‐specific parameters (increased tissue elastance and tissue damping) but less pronounced in females. BLM‐challenged mice showed a time‐of‐day response in lung function at ZT0 versus ZT12, which was pronounced in the ZT0 BLM group. Overall, these findings provide a comprehensive analysis of altered lung function in female and male mice and the time‐of‐day difference in lung function parameters following BLM‐induced lung fibrosis.

Repetitive invasive lung function maneuvers do not accentuate experimental fibrosis in mice

“…In the current study, we used female mice mainly because of housing reasons. Some studies reported sex-dependent differences in LFT parameters in the bleomycin model of lung fibrosis 25 , 26 . However, in a previous study of our group, we did not observe any differences in lung function in AdTGF-β1 treated male and female mice after a single LFT 22 , suggesting no impact of sex in the currently employed fibrosis model.…”