Astaxanthin attenuates pulmonary fibrosis through lncITPF and mitochondria‐mediated signal pathways

Abstract

Pulmonary fibrosis is a chronic interstitial lung disease characterized by pulmonary epithelial injury, fibroblast activation, extracellular matrix deposition, and tissue structure destruction. However, an effective drug treatment remains unavailable. Therefore, studying the mechanism of pulmonary fibrogenesis and finding effective drugs have become important problems in the field of respiratory diseases. Pulmonary fibrosis is typically characterized by activated fibroblast proliferation and migration. Hence, abnormality in activated fibroblast proliferation and migration is a major concern for treating pulmonary fibrosis. Long noncoding RNA (lncRNA) is an enigmatic subclass of ncRNA that regulates various fundamental biological processes and participates in disease occurrence and development. However, studies on lncRNA as the therapeutic target of drug action are rarely reported. Our group first identified differentially expressed lncRNAs and revealed that lncITPF is a highly upregulated lncRNA in lung fibrosis. In particular, lncITPF is detected in the blood of patients with idiopathic pulmonary fibrosis. Clinical analysis shows that lncITPF is positively correlated with the degree of fibrosis. The receiver operating characteristic (ROC) curve indicates that the specificity and sensitivity values are 95.0 and 64.3, respectively. The area under the ROC curve is 0.804, indicating that lncITPF can be a diagnostic biomarker for IPF. However, whether lncITPF is effective as a therapeutic target of drug action against pulmonary fibrosis remains unclear. In this study, lncITPF acting as the therapeutic target of astaxanthin was explored in depth. The findings elucidated that astaxanthin blocks the activated fibroblast proliferation and migration through lncITPF and mitochondria‐mediated signal pathways to alleviate pulmonary fibrogenesis.

Lutein attenuates angiotensin II- induced cardiac remodeling by inhibiting AP-1/IL-11 signaling

“…In addition, Ang II induced the transdifferentiation of CFs into myofibroblasts, which exhibit high proliferation and migration, resulting in excessive production of ECM and fibrosis, which is a sign of pathological remodeling [ 35 ]. Recent studies indicate that carotenoids exhibit therapeutic effects against fibrotic disorders, including chronic kidney disease, pulmonary fibrosis and liver disease [ [43] , [44] , [45] ]. In this study, we found that lutein suppressed proliferation, migration and differentiation in vitro and prevented Ang II-induced pathological cardiac fibrosis in vivo.…”

Long non‐coding RNAs: Promising new targets in pulmonary fibrosis

“…63,64 Other drugs targeting lncRNAs, such as astaxanthin, angelica sinensis polysaccharide, astragaloside IV and astilbin, are under investigation at present. [101][102][103][104] Astaxanthin alleviates lung fibrosis by blocking Smad3 nuclear translocation to inhibit lncITPF transcription. 101 lncDANCR mediates angelica sinensis polysaccharide-induced suppression of IPF via upregulation of FOXO3 protein levels in an AU-binding factor 1-dependent manner.…”

“…[101][102][103][104] Astaxanthin alleviates lung fibrosis by blocking Smad3 nuclear translocation to inhibit lncITPF transcription. 101 lncDANCR mediates angelica sinensis polysaccharide-induced suppression of IPF via upregulation of FOXO3 protein levels in an AU-binding factor 1-dependent manner. 102 Astragaloside IV treatment increases lncsirt1 AS and lncsirt1 F I G U R E 1 Molecular mechanisms of lncRNAs and lncRNA-based clinical applications in pulmonary fibrosis.…”

Genomics of Human Fibrotic Diseases: Disordered Wound Healing Response

“…Njock et al [ 217 ] performed miRNA expression profiling of sputum-derived exosomes from IPF patients, identifying 21 miRNAs that were differentially expressed, including upregulated miR-142-3p and miR-33a-5p and downregulated let-7d-5p. In addition to miRNAs, long non-coding RNAs are emerging as contributors to IPF development (reviewed in [ 218 ]); as one example, lncITPF is highly upregulated in lung fibrosis [ 219 ].…”