p38 MAPK and Epigenetic Regulation of Fibrotic Genes in Lung Cell Senescence | Aging-US

Aging-US #published this #research paper on March 3, 2026, in Volume 18, titled “P38 MAPK is involved in epigenetic regulation of fibrotic genes in replication induced senescence in lung fibroblasts" by #researchers from the Department of Biomedical and Translational Sciences, Eastern Virginia Medical School, Macon & Joan Brock Virginia Health Sciences at Old Dominion University, Norfolk 23510, VA. @ODU #aging #senescence #IPF #lungs #p38 #fibroblast #openaccess #openscience #peerreviewed #journal #publishing #meded DOI: https://doi.org/10.18632/aging.206357 Corresponding author: Yan Y Sanders - sandery@odu.edu Abstract Fibroblast activation is essential for tissue repair following injury; however, prolonged activation drives pathological fibrosis. Idiopathic pulmonary fibrosis (IPF), a progressive and age-associated lung disease, is characterized by aberrant fibroblast activation, with increasing evidence implicating senescent and near-senescent fibroblasts in its pathogenesis. However, the underlying mechanisms remain poorly defined. In this study, we investigated whether histone modification is involved in TGF-β1 treated lung fibroblasts and contributes to the fibrotic phenotype. Human IMR90 lung fibroblasts at low and high population doubling levels (LPDL and HPDL), as well as primary IPF fibroblasts, were used in this study. In response to TGF-β1, both LPDL and HPDL fibroblasts upregulated profibrotic genes, including α-smooth muscle actin (α-SMA) and Collagen type III alpha 1 (Col3A1). Compared with LPDL fibroblasts, HPDL fibroblasts exhibited a delayed and sustained p38 MAPK response. Pharmacological inhibition of p38 MAPK significantly reduced α-SMA and Col3A1 expression in both TGF-β1-stimulated fibroblasts and primary IPF cells. Mechanistically, TGF-β1-induced expression of α-SMA and Col3A1 was mediated by histone H4K16 acetylation (H4K16ac), which was enriched at gene promoter regions and attenuated by p38 MAPK inhibition. These findings suggest that a p38 MAPK–dependent epigenetic mechanism is involved in fibroblast activation, supporting the therapeutic potential of p38 MAPK inhibition for treating age-related fibrotic diseases such as IPF. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206357 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, fibroblast activation, p38 MAPK, lung fibrosis, H4K16Ac To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM