PPI network and Hubgenes
All DEGs were analyzed by STRING
online database. Using the Cytoscape software, 49 DEGs were mapped to
the PPI network (Fig 2 ). The top 10 Hub genes
referred to IL10, IFNG, Fos, IL19,
NPY, Cnr1, PDE4B, MMP13, Rtn1, UCHL1, which were assessed and ranked by
the plugin cytoHubba in Cytoscape (Table2). Phosphodiesterase
4B (PDE4B), a member of phosphodiesterase (PDEs) family, serves as a
selectively hydrolytic enzyme of second signal messenger cAMP(cyclic
adenosine monophosphate)[15,25], playing a vital role in signal
transduction of inflammation[15]. The inhibitor of PDE4 has
demonstrated a prominent validity in treating inflammatory disease such
as asthma, chronic obstructive pulmonary disease, inflammatory bowel
disease, atopic dermatitis, rheumatoid arthritis, and other
disease[15,26]. cAMP-activated PKA exerts an effect to inhibit
NFκB signaling
pathway [10,27,28]. PDE4B deficit macrophage exhibit the decreased
NFκB activation and reactive oxygen species level induced by LPS, and
the suppressed inflammatory response [14,29,30]. The
anti-inflammatory ability of NR4a1 has association with NFκB signaling
pathway. Therefore, we speculate that NR4a1 may regulate the PED4B
expression with anti-inflammatory function and a close relation of
NR4a1-regulated PDE4B to cAMP-PKA signaling and NFκB signaling pathway.