Haematococcus pluvialis ameliorates renal fibrosis by restoring mitophagy via PINK1-Parkin-p62-LC3 signaling.

Renal fibrosis is a key pathological process of chronic kidney disease (CKD) and is associated with epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction. Haematococcus pluvialis (H. pluvialis), a unicellular green alga, is rich in natural antioxidants like astaxanthin and unsaturated fatty acids. This study aimed to explore the renal protective effects and the potential mechanisms of H. pluvialis in vivo and in vitro. The bioinformatics analysis combined with in vivo and in vitro studies revealed that H. pluvialis attenuated renal fibrosis by restoring mitophagy and reversing EMT. For in vivo experiments, H. pluvialis reduced renal ECM deposition and improved renal injury in the unilateral ureteral obstruction (UUO) rats. RNA-seq analysis and in vitro studies showed that H. pluvialis reversed the TGF-β1-induced EMT in HK-2 cells and improved mitochondrial energy metabolism. Immunofluorescence and molecular docking results suggested that H. pluvialis, especially astaxanthin and trans-3-indoleacrylic acid in it, restored mitophagy via PINK1-Parkin-p62-LC3 signaling and reduced pro-fibrotic factor secretion in HK-2 cells. This study supports the development of H. pluvialis as a functional food for CKD management, providing a new strategy to ameliorate renal fibrosis.