Inhibition of FABP4 attenuates hyperoxia-induced lung injury and fibrosis via inhibiting TGF-β signaling in neonatal rats

Research output: Contribution to journalArticlepeer-review

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by interrupted alveologenesis and alveolar simplification caused by oxygen therapy in premature infants. Metabolic dysfunction is involved in the pathogenesis of BPD. Fatty acid-binding protein 4 (FABP4) is significantly increased in specific lung tissues in patients with BPD. Therefore, we investigated whether BMS309403, an FABP4 inhibitor that can mitigate tissue fibrosis, can regulate pulmonary fibrotic processes in newborn rats exposed to hyperoxia. Newborn rat pups were exposed to room air (RA; 21% O2) or 85% O2 from 5 to 14 days of age and were then allowed to recover in RA until 29 days of age. They received intraperitoneal injection with placebo (phosphate-buffered saline [PBS]) or BMS 309403 (0.5 mg or 1.0 mg kg−1 d−1) every other day from 4 to 14 days of age then were divided into O2 plus PBS or low dose or high dose and RA plus PBS or low dose or high dose groups. We assessed lung histology and evaluated lung collagen I, FABP4 as well as TGF-β1 expression at 14 and 29 days of age. In the hyperoxia injury-recovery model, prophylactic BMS309403 treatment reduced mean linear intercept values and FABP4 expression (p < 0.001). Prophylactic BMS309403 treatment mitigated pulmonary fibrosis and TGF-β1 expression immediately after hyperoxia exposure (p < 0.05). The attenuation of hyperoxia-induced alveolar developmental impairment and pulmonary fibrosis by FABP4 inhibition indicated that such inhibition has potential clinical and therapeutic applications.

Original languageEnglish
Pages (from-to)1509-1520
Number of pages12
JournalJournal of Cellular Physiology
Volume237
Issue number2
DOIs
Publication statusPublished - Feb 2022

Keywords

  • bronchopulmonary dysplasia
  • fatty acid binding protein
  • fatty acid binding protein inhibitor
  • fibroblast

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Inhibition of FABP4 attenuates hyperoxia-induced lung injury and fibrosis via inhibiting TGF-β signaling in neonatal rats'. Together they form a unique fingerprint.

Cite this