PI3K/Akt in IPF: untangling fibrosis and charting therapies

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease characterized by abnormal epithelial repair, persistent inflammation, and excessive extracellular matrix deposition, leading to irreversible scarring and respiratory failure. Central to its pathogenesis is the dysregulation o...

Full description

Saved in:
Bibliographic Details
Main Authors: Janki Bhatt, Alessandra Ghigo, Emilio Hirsch
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549277/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849769944759140352
author Janki Bhatt
Janki Bhatt
Alessandra Ghigo
Alessandra Ghigo
Emilio Hirsch
Emilio Hirsch
author_facet Janki Bhatt
Janki Bhatt
Alessandra Ghigo
Alessandra Ghigo
Emilio Hirsch
Emilio Hirsch
author_sort Janki Bhatt
collection DOAJ
description Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease characterized by abnormal epithelial repair, persistent inflammation, and excessive extracellular matrix deposition, leading to irreversible scarring and respiratory failure. Central to its pathogenesis is the dysregulation of the PI3K/Akt signaling pathway, which drives fibroblast activation, epithelial-mesenchymal transition, apoptosis resistance, and cellular senescence. Senescent cells contribute to fibrosis through the secretion of pro-inflammatory and profibrotic factors in the senescence-associated secretory phenotype (SASP). Current antifibrotic therapies, Nintedanib and Pirfenidone, only slow disease progression and are limited by side effects, highlighting the need for novel treatments. This review focuses on the role of PI3K/Akt signaling in IPF pathogenesis, its intersection with inflammation and fibrosis, and emerging therapeutic approaches targeting molecules along this pathway.
format Article
id doaj-art-f58eaa0db80f468cb1cd627e1d3c6713
institution DOAJ
issn 1664-3224
language English
publishDate 2025-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-f58eaa0db80f468cb1cd627e1d3c67132025-08-20T03:03:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15492771549277PI3K/Akt in IPF: untangling fibrosis and charting therapiesJanki Bhatt0Janki Bhatt1Alessandra Ghigo2Alessandra Ghigo3Emilio Hirsch4Emilio Hirsch5Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center “Guido Tarone”, University of Turin, Turin, ItalyKither Biotech S.r.l., Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center “Guido Tarone”, University of Turin, Turin, ItalyKither Biotech S.r.l., Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center “Guido Tarone”, University of Turin, Turin, ItalyKither Biotech S.r.l., Turin, ItalyIdiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease characterized by abnormal epithelial repair, persistent inflammation, and excessive extracellular matrix deposition, leading to irreversible scarring and respiratory failure. Central to its pathogenesis is the dysregulation of the PI3K/Akt signaling pathway, which drives fibroblast activation, epithelial-mesenchymal transition, apoptosis resistance, and cellular senescence. Senescent cells contribute to fibrosis through the secretion of pro-inflammatory and profibrotic factors in the senescence-associated secretory phenotype (SASP). Current antifibrotic therapies, Nintedanib and Pirfenidone, only slow disease progression and are limited by side effects, highlighting the need for novel treatments. This review focuses on the role of PI3K/Akt signaling in IPF pathogenesis, its intersection with inflammation and fibrosis, and emerging therapeutic approaches targeting molecules along this pathway.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549277/fullidiopathic pulmonary fibrosisPI3K/AKTinflammationfibrosissenescencePI3K inhibitor
spellingShingle Janki Bhatt
Janki Bhatt
Alessandra Ghigo
Alessandra Ghigo
Emilio Hirsch
Emilio Hirsch
PI3K/Akt in IPF: untangling fibrosis and charting therapies
Frontiers in Immunology
idiopathic pulmonary fibrosis
PI3K/AKT
inflammation
fibrosis
senescence
PI3K inhibitor
title PI3K/Akt in IPF: untangling fibrosis and charting therapies
title_full PI3K/Akt in IPF: untangling fibrosis and charting therapies
title_fullStr PI3K/Akt in IPF: untangling fibrosis and charting therapies
title_full_unstemmed PI3K/Akt in IPF: untangling fibrosis and charting therapies
title_short PI3K/Akt in IPF: untangling fibrosis and charting therapies
title_sort pi3k akt in ipf untangling fibrosis and charting therapies
topic idiopathic pulmonary fibrosis
PI3K/AKT
inflammation
fibrosis
senescence
PI3K inhibitor
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549277/full
work_keys_str_mv AT jankibhatt pi3kaktinipfuntanglingfibrosisandchartingtherapies
AT jankibhatt pi3kaktinipfuntanglingfibrosisandchartingtherapies
AT alessandraghigo pi3kaktinipfuntanglingfibrosisandchartingtherapies
AT alessandraghigo pi3kaktinipfuntanglingfibrosisandchartingtherapies
AT emiliohirsch pi3kaktinipfuntanglingfibrosisandchartingtherapies
AT emiliohirsch pi3kaktinipfuntanglingfibrosisandchartingtherapies