Immune-complex glomerulonephritis (ICGN) is a major cause of
nephrotic syndrome in adults and children. Cationic BSA (c-BSA)
intravenous injection could produce significant
albuminuria within a short time, and is a suitable in vivo experimental animal model to investigate the pathophysiology of ICGN and for drug screening, but lack of thorough study to clarify its dynamic pathophysiological alteration so far, as well as detailed changes in
mRNA and
LncRNA levels. The purpose of this study is to investigate the dynamic alteration in renal function, lipid metabolism and histopathology during the progress of c-BSA induced ICGN.
RNA sequencing was used to identified differentially expressed
mRNA and
LncRNA in kidney cortex of ICGN. Results demonstrated that c-BSA induced ICGN model could completely exhibit clinical features of immune-mediated
nephrotic syndrome with gradual declining renal function, and increased
albuminuria and deteriorated histopathological
injuries. The correlation analysis suggested that complement activation was the most key
element in mediating of ICGN.
RNA sequencing using rat kidney tissues combined with Gene Expression Omnibus (GEO) data of human
glomerulonephritis showed the most enriched KEGG pathways in ICGN were
Toll-like receptor signaling pathway, B cell receptor and Focal adhesion. The differential lncRNAs in ICGN rats were also screened, and the
lncRNA-
mRNA co-expression network was constructed to clarify
lncRNA role in molecular mechanism of ICGN progression. Their human homogenous lncRNAs were also identified, such as ST3GAL5-AS1 and DIO3OS, which provide the potential
lncRNA targets to treat ICGN. All the differential LncRNAs in ICGN kidneys caused by MMF were also identified and provided another possible pharmacological mechanism of MMF through
lncRNA regulation. In summary, the current study firstly described the dynamic physiological changes of c-BSA induced ICGN, identified most key KEGG pathways, and provided
lncRNA-
mRNA regulatory network in ICGN.