C-phycocyanin reinforces autophagy to block pulmonary fibrogenesis by inhibiting lncIAPF biogenesis

• DOI: 10.1007/s12272-024-01508-y
• Publication Date: 2024-07-22T22:01:47Z
• Authors: Wenjie Hu; Yujie Wang; Huiling Yang; Leiming Zhang; Bo Liu; Yunxia Ji; Xiaodong Song; Changjun Lv; Songzi Zhang
• Keywords: Male; Mice, Inbred C57BL; 0301 basic medicine; Mice; 03 medical and health sciences; Pulmonary Fibrosis; Autophagy; Phycocyanin; Humans; Animals; RNA, Long Noncoding; Research Article

AbstractPulmonary 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.