Related Experiment Video
Updated: Oct 15, 2026
Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models
Published on: June 20, 2025
Transcriptional factor KLF9 in pulmonary fibrosis: from molecular mechanisms to precision intervention-a narrative
Ayinuer Kelimujiang1, Yanmei Lu1
1Department of Cardiac Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Background And Objective:
Pulmonary fibrosis (PF) is a devastating and progressive respiratory disease characterized by extracellular matrix (ECM) remodelling and functional decline, yet current therapeutic options remain limited. Recent studies have highlighted the critical, albeit complex, role of Krüppel-like factor 9 (KLF9) in the pathogenesis of PF. This review aims to comprehensively integrate the existing fragmented mechanistic evidence, delineate the differential regulatory networks of KLF9, and outline forward-looking strategies to promote the transition of KLF9 from a mechanistic candidate molecule to a clinically translatable target.
Methods:
A comprehensive literature search was conducted on databases including PubMed, Web of Science, and Embase for articles published up to March 14, 2026. The search focused on keywords such as ("pulmonary fibrosis" OR "idiopathic pulmonary fibrosis" OR "lung fibrosis") AND ("Krüppel-like factor 9" OR "KLF9" OR "BTEB1").
Key Content And Findings:
Evidence indicates that KLF9 exhibits differential regulatory networks in alveolar epithelial cells, fibroblasts, and macrophages. Based on its functional paradox across diverse cell types, conventional systemic interventions targeting KLF9 face inherent limitations, including the "undruggable" nature of transcription factors and physical barriers in fibrotic lungs. To overcome these obstacles, advanced targeted strategies are required.
Conclusions:
While KLF9 plays a pivotal role in the fibrotic microenvironment, realizing its therapeutic potential necessitates a paradigm shift in intervention methods. Forward-looking strategies, including single-cell/spatial multi-omics analysis, ligand-modified inhaled nano-delivery, and stage-dependent dynamic dosing systems [such as proteolysis-targeting chimera (PROTAC) technology], represent promising avenues for precise KLF9 targeting in PF.
