ITGAM is the hub gene potentially activating FAK pathway in
hyperuricemia-related CKD
We combined mRNA and protein sequencing data and picked out those DEGs
at both levels in kidneys of mice (Figure 2A &Supplementary Figure 1A ). The details about digging out hub
genes and pathways related are presented in Supplementary Figure
1B. In brief, we performed the enrichment analysis and canonical
pathway analysis using up-regulated and down-regulated DEGs separately
and presented functional characteristics accordingly
(Supplementary Figure 2 ). After MCODE analysis, we picked out
the top 5 clusters consisting of 334 DEGs (Supplementary Figure
3 ) followed by CentiScaPe analysis to obtain 49 hub genes. By matching
the top enrichment pathways with hub genes, we found two most
significantly enriched genes- Itgam and Itgb2, that encoded two subunits
constituting the heterodimer Mac-1 (Figure 2B ). The key
functional role of Itgam was also highlighted by IPA biomarker analysis,
with ITGAM ranking the 1st at both mRNA and protein
levels. Itgam in day-21 group was up-regulated to 19-folds and 3.3-fold
of that in day-0 group at mRNA and protein level, respectively
(Figure 2C ). To explore key pathways that were potentially
regulated by ITGAM, we selected significant genes positively correlated
with Itgam at mRNA and protein level, and performed the KEGG pathway
enrichment analysis (Figure 2D ). Since there is an abundance of
literature on tyrosine kinases as major signal transducers by
integrins(Berton & Lowell, 1999), we hypothesized that FAK signaling
was activated by ITGAM in kidneys of hyperuricemia-related CKD mice
(Figure 2E ).