GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330802/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330802GEOGSEfalseMesothelial plasticity regulates lung mechanical homeostasis in regeneration and fibrosisTissue mechanical adaptation is fundamental to organ development, regeneration and disease, yet the cellular mechanisms that regulate tissue mechanical adaptation remain poorly understood. Here we show that mesothelial cells are key regulators of lung mechanical adaptation. Following pneumonectomy, elevated stretch activates YAP and induces a transient fibroblast-like mesothelial cell state (F-LMC) characterized by reduced mesothelial identity, increased fibroblast feature, and extracellular-matrix remodeling at the pleural surface. Yap deletion suppresses F-LMC formation, resulting in lung overinflation and defective regeneration following pneumonectomy. By contrast, in fibrotic lungs, this mesothelial remodeling program is aberrantly activated and restricts lung inflation. Inhibition of this maladaptive response prevents the decline in lung capacity following bleomycin-induced pulmonary fibrosis. Collectively, our findings redefine the mesothelium as a mechanosensitive regulator of organ-scale mechanical adaptation and reveal how pleural surface remodeling controls tissue mechanics during regeneration and disease.2026/09/25GSE330802GSM9733022GSM973302124247330802Mus musculus