Stearic acid attenuates profibrotic signalling in idiopathic pulmonary fibrosis

Abstract

Background and objective: Lipid metabolism dysregulation has been implicated in the pathogenesis of IPF; however, the roles of most lipid metabolites in lung fibrosis remain unexplored. Therefore, we aimed to identify changes in lipid metabolites in the lung tissues of IPF patients and determine their roles in pulmonary fibrosis. Methods: Free fatty acids in the lung tissues of IPF patients and controls were quantified using a metabolomic approach. The roles of free fatty acids in fibroblasts or epithelial cells treated with TGF-β1 were evaluated using fibrotic markers. The antifibrotic role of stearic acid was also assessed in a bleomycin-induced lung fibrosis mouse model. Protein levels in cell lysates or tissues were measured by western blotting. Results: The levels of stearic acid were lower in IPF lung tissues than in control lung tissues. Stearic acid significantly reduced TGF-β1-induced α-SMA and collagen type 1 expression in MRC-5 cells. Furthermore, stearic acid decreased the levels of p-Smad2/3 and ROS in MRC-5 cells treated with TGF-β1 and disrupted TGF-β1-induced EMT in Beas-2B cells. Stearic acid reduced the levels of bleomycin-induced hydroxyproline in a mouse model. Conclusion: Changes in the free fatty acid profile, including low levels of stearic acid, were observed in IPF patients. Stearic acid may exert antifibrotic activity by regulating profibrotic signalling.

The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis

“…S4g, h ) of Beas-2B cells. We next analyzed the mRNA expression of SLUG and VIM , which are TGF-β1-induced EMT-related genes 30 , 31 . TPPU significantly inhibited TGF-β1-induced mRNA levels of SLUG and VIM (Fig.…”

“…Recent studies suggested that IPF develops as a result of an aberrant wound healing response after recurrent alveolar injury 2 and that dysregulation of lipid metabolism is involved in the pathogenesis of IPF 6 , 7 , 31 . EETs serve as important antifibrotic lipid mediators in fibrotic diseases such as pulmonary and renal fibrosis 17 , 18 , 33 .…”

Metabolomics as a Tool to Study Underused Soy Parts: In Search of Bioactive Compounds

“…Shikimic acid, an example of an organooxygen compound, was linked to therapeutic effects in osteoarthritis [135]. Metabolites of other classes, such as succinic and stearic acids, presented an apoptotic effect in T-cell acute lymphoblastic leukemia and antifibrotic activity, respectively [136,137]. Flavonoids and isoflavonoids, such as 7,4 -dihydroxyflavone and glycitin, presented activity against lung diseases [138,139].…”

A Ferroptosis-Related Gene Signature for Lung Function and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis

“…ACSL1 plays a key role in fatty acid metabolism. Studies have found that lipid metabolism dysregulation play an important role in the pathogenesis of IPF [44,45]. In addition, the levels of stearic acid (the one of fatty acid) is down-regulated in IPF lung tissues than in control lung tissues, and further study found that stearic acid had anti brotic activity [45].…”