AI Article Synopsis

  • Idiopathic pulmonary fibrosis (IPF) is a serious and progressive lung disease linked to changes in metabolism, mitochondria, and cellular cleanup processes in lung cells.
  • The microRNA-33 (miR-33) family regulates metabolism and impacts macrophage responses, showing increased levels in lung fluid from IPF patients compared to healthy individuals.
  • By removing miR-33 in macrophages, researchers demonstrated reduced lung fibrosis and inflammation, suggesting that targeting miR-33 could offer a new treatment strategy for IPF.

Article Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Recent findings have shown a marked metabolic reprogramming associated with changes in mitochondrial homeostasis and autophagy during pulmonary fibrosis. The microRNA-33 (miR-33) family of microRNAs (miRNAs) encoded within the introns of sterol regulatory element binding protein (SREBP) genes are master regulators of sterol and fatty acid (FA) metabolism. miR-33 controls macrophage immunometabolic response and enhances mitochondrial biogenesis, FA oxidation, and cholesterol efflux. Here, we show that miR-33 levels are increased in bronchoalveolar lavage (BAL) cells isolated from patients with IPF compared with healthy controls. We demonstrate that specific genetic ablation of miR-33 in macrophages protects against bleomycin-induced pulmonary fibrosis. The absence of miR-33 in macrophages improves mitochondrial homeostasis and increases autophagy while decreasing inflammatory response after bleomycin injury. Notably, pharmacological inhibition of miR-33 in macrophages via administration of anti-miR-33 peptide nucleic acids (PNA-33) attenuates fibrosis in different in vivo and ex vivo mice and human models of pulmonary fibrosis. These studies elucidate a major role of miR-33 in macrophages in the regulation of pulmonary fibrosis and uncover a potentially novel therapeutic approach to treat this disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977502PMC
http://dx.doi.org/10.1172/jci.insight.158100DOI Listing

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