Transcriptomic analysis of Chinese cordyceps extract regulate adriamycin-induced podocyte injury

Nephrotic syndrome is one of the well-known presentations of adult and paediatric renal disease. Podocyte injury plays a vital role in this disease, and sustained podocyte damage leads to the disorganization of the cytoskeleton, foot process fusion, and subsequently the emergence of proteinuria. Podocyte protection is of considerable significance to prevent or delay nephrotic syndrome process. Chinese cordyceps is extensively used to treat chronic renal diseases and accelerates the recovery of renal function via alleviating podocyte injury. In the present study, podocyte protective activity of Chinese cordyceps extracts by different solvents was demonstrated, based on adriamycin-induced podocyte cell model, and the possible molecular mechanism on the podocyte protection was explored via RNA-seq analysis. Among Chinese cordyceps extracts, water-soluble components reached over 90% by weight, mainly including proteins, polysaccharides, adenosine, and nucleosides. n-hexane extract (HCC) exerted podocyte protective bioactivity probably via regulating cellular metabolism to provide sufficient energy and metabolites for cell repair and growth, regulating steroid hormone biosynthesis, promoting the development of secondary sexual characteristics, and ensuring skeletal health. The water extract precipitated with 20% ethanol (W1CC) protect podocytes probably by enhancing the expression of genes associated with the one-carbon pool by folate pathway, regulating endocrine system and related genes to against fibrosis, and preserving cardiovascular health by regulating the expression levels of apelin signaling pathway to stabilize blood pressure and forestall cardiac fibrosis, regulating genes associated with specific immune pathways. The remaining extract precipitated with 80% ethanol (W5CC) modulated the proliferation and survival of the podocytes by regulating metabolic pathways, and partially restores the expression of human disease pathways related genes. The present data provides informative support for using Chinese cordyceps to treat nephrotic syndrome in clinical application and a reference for further mechanism research.