Pulmonary fibrosis is a chronic and irreversible progressive lung disease caused by various factors, such as age and environmental pollution. With countries stepping into an aging society and the seriousness of environmental pollution caused by global industrialization, the incidence of pulmonary fibrosis is annually increasing. However, no effective drug is available for pulmonary fibrosis treatment. C-phycocyanin (C-PC), extracted from blue-green algae, has good water solubility and antioxidation. This study elucidated that C-PC reinforces autophagy to block pulmonary fibrogenesis by inhibiting long noncoding RNA (lncRNA) biogenesis in vivo and in vitro. Cleavage under targets and release using nuclease (CUT & RUN)-PCR, co-immunoprecipitation (Co-IP), and nuclear-cytoplasmic separation experiments clarified that C-PC blocked the nuclear translocation of activating transcription factor 3 (ATF3) to prevent the binding between ATF3 and transcription factor Smad3, thereby hindering lncIAPF transcription. Human antigen R (HuR) truncation experiment and RNA binding protein immunoprecipitation (RIP) were then performed to identify the binding domain with lncIAPF in the 244-322 aa of HuR. lncIAPF exerted its profibrogenic function through the binding protein HuR, a negative regulator of autophagy. In summary, C-PC promoted autophagy via down-regulating the lncIAPF-HuR-mediated signal pathway to alleviate pulmonary fibrosis, showing its potential as a drug for treating pulmonary fibrosis. Exploring how C-PC interacts with biological molecules will help us understand the mechanism of this drug and provide valuable target genes to design new drugs.
Keyphrases
- pulmonary fibrosis
- binding protein
- transcription factor
- signaling pathway
- endoplasmic reticulum stress
- dna binding
- long noncoding rna
- cell death
- human health
- oxidative stress
- heavy metals
- genome wide identification
- epithelial mesenchymal transition
- pulmonary hypertension
- risk assessment
- endothelial cells
- particulate matter
- multiple sclerosis
- adverse drug
- long non coding rna
- health risk assessment
- gene expression
- transforming growth factor
- dna methylation
- emergency department
- liquid chromatography
- life cycle
- drinking water
- climate change
- water quality
- nucleic acid
- bioinformatics analysis