Figure 2 Icariin alleviated inflammatory responses and oxidative
stress in UUO mice. (A) Gene Ontology (GO) enrichment analysis of
differentially expressed genes between the sham and UUO mice. (B)
Heatmap of inflammatory response-related genes expression profiles of
different groups based on the RNA-seq data set. The quantitative
value=log10 FPKM. (C) Heatmap of key
oxidoreductase-related gene expression of different groups based on the
RNA-seq data set. The quantitative value=log10 FPKM. (D)
Quantitative real-time PCR analysis of TNF-α, IL-1β and IL-6 mRNA
levels. (E) MDA levels in the kidney. (F) SOD activity in the kidney.
(G) Representative IHC images and quantification of F4/80 expression in
the kidney from different groups. * p < 0.05, ** p <
0.01.
Icariin restored mitochondrial homeostasis in UUO mice.
Emerging discoveries demonstrate that
mitochondrial
damage is a critical step to trigger inflammation and oxidative stress
in fibrotic diseases19,20. Our RNA-seq data also
indicated that mitochondrion-related genes were significantly
differentially expressed between the sham and UUO mice (Figure 2A). To
further investigate whether icariin attenuated UUO-induced oxidative
stress and inflammation by maintaining mitochondrial homeostasis, we
then detected mitochondrial changes. The immunofluorescence staining of
TOMM20, an outer mitochondrial membrane marker, revealed a significant
reduction of mitochondria in kidneys from UUO mice (Figure 3A).
Additionally, TEM observed evident mitochondrial damages, characterized
by pronounced swelling, cristae loss, and mitochondrial membrane rupture
in UUO mice (Figure 3B). However, treatment with icariin effectively
alleviated these changes, indicating that icariin can improve
UUO-induced mitochondrial abnormalities.