Table I.
KEGG pathways dysregulated by physical exercise in mice with proteoglycan-induced arthritis.
| KEGG pathway (number of genes) | Genes (p-value*) |
|---|---|
| Upregulated | |
| Spliceosome (12) | Ddx39b, Thoc3, Cdc5l, Hspa1a, Hnrnpa1, Prpf18, Prpf6, Snrnp27, Snrpe, Sf3a2, Sf3a3, Smndc1 (p = 0.010)† |
| Nonalcoholic fatty liver disease (13) | Ndufa1, Ndufa12, Ndufa7, Ndufab1, Ndufc1, Ndufs3, Ndufs4, Cox8b, Cox5a, Eif2s1, Jun, Ppara, Uqcrq (p = 0.130)† |
| Oxidative phosphorylation (12) | Atp5j, Atp5l, Ndufa1, Ndufa12, Ndufa7, Ndufab1, Ndufc1, Ndufs3, Ndufs4, Cox8b, Cox5a, Uqcrq (p = 0.014)† |
| Huntington's disease (15) | Atp5j, Ndufa1, Ndufa12, Ndufa7, Ndufab1, Ndufc1, Ndufs3, Ndufs4, Cltb, Cox8b, Cox5a, Ift57, Pparg, Polr2i, Uqcrq (p = 0.015)† |
| Glutathione metabolism (7) | Anpep, Ggct, Ggt1, Gsto2, Gsta3, Gpx5, Mgst3 (p = 0.015)† |
| Parkinson's disease (12) | Atp5j, Ndufa1, Ndufa12, Ndufa7, Ndufab1, Ndufc1, Ndufs3, Ndufs4, Cox8b, Cox5a, Uqcrq, Uba1y (p = 0.022)† |
| Metabolic pathways (61) | Papss2, Atp5j, Atp5l, Coasy, Ndufa1, Ndufa12, Ndufa7, Ndufab1, Ndufc1, Ndufs3, Ndufs4, B3gnt2, Acaa1a, Acaa2, Acsm3, Ada, Anpep, Aldh1a3, Aldh1a7, Acy1, Alox12b, Arg1, Aanat, Bckdha, Cmpk1, Cyp2c68, Cyp24a1, Cox8b, Cox5a, Coq7, Dgke, Enpp1, Extl3, Galc, Ggt1, Gne, Gad2, Gpat4, Inpp1, Idh3g, Kmo, Lpcat1, Mecr, Ebp, Pigc, Pmvk, Pola2, Pold1, Pold2, Pole4, Polr2i, Prodh, Sds, Sphk1, Tyms, Tkt, Tpi1, Uqcrq, Upp1, Uro (p = 0.025)† |
| Pyrimidine metabolism (9) | Cmpk1, Entpd8, Pola2, Pold1, Pold2, Pole4, Polr2i, Tyms, Upp1 (p = 0.036)† |
| Renin-angiotensin system (5) | Atp6ap2, Anpep, Agtr2, Ctsg, Lnpep (p = 0.039)† |
| DNA replication (5) | Pola2, Pold1, Pold2, Pole4, Ssbp1 (p = 0.039)† |
| Mismatch repair (4) | Msh2, Pold1, Pold2, Ssbp1 (p = 0.046)† |
| Downregulated | |
| Haematopoietic cell lineage (14) | Cd2, Cd44, Cd59a, Gp1bb, Il11ra1, Il11, Il2rα, Il3, Il4ra, Il4, Il5, Il6ra, Kitl, Tfrc (p < 0.001)† |
| JAK-STAT signalling pathway (16) | Crebbp, Ctf1, Il11ra1, Il11, Il2rα, Il2rβ, Il3, Il4ra, Il4, Il5, Il6ra, Lif, Stam2, Socs4, Socs5, Akt (p = 0.004)† |
| Notch signalling pathway (8) | Crebbp, Aph1c, Dll3, Dtx2, Dvl2, Dvl3, Numbl, Rbpj (p = 0.008)† |
| GABAergic synapse (11) | Cacna1s, Gabra2, Gabrb1, Gabrb3, Gabrg2, Gabrg3, Gnb5, Gng12, Gng2, Gngt2, Slc32a1 (p = 0.009)† |
| Retrograde endocannabinoid signalling (12) | Cacna1s, Gabra2, Gabrb1, Gabrb3, Gabrg2, Gabrg3, Gnb5, Gng12, Gng2, Gngt2, Slc17a7, Slc32a1. (p = 0.010)† |
| Nicotine addiction (7) | Gabra2, Gabrb1, Gabrb3, Gabrg2, Gabrg3, Slc17a7, Slc32a1 (p = 0.012)† |
| Calcium signalling pathway (17) | Adra1b, Cacna1s, Camk2a, Camk2d, Camk4, Ednra, Ednrb, Erbb4, Gnal, Lhcgr, Plcd3, Plcd4, Phka1, Ptafr, P2rx4, Ryr1, Vdac1 (p = 0.013)† |
| Cytokine-cytokine receptor interaction (21) | Cd40lg, Acvr2b, Bmpr1a, Ctf1, Ccl27a, Ccr6, Cxcl12, Cxcl9, Edar, Il11ra1, Il11, Il2rα, Il2rβ, Il3, Il4ra, Il4, Il5, Il6ra, Kitl, Lif, Tnfrsf17 (p = 0.014)† |
| Signalling pathways regulating pluripotency of stem cells (14) | Bmi1, Acvr2b, Bmpr1a, Dvl2, Dvl3, Esrrb, Esx1, Fgfr2, Fzd7, Hand1, Lif, Pcgf5, Akt3 (p = 0.015)† |
| Asthma (5) | Cd40lg, H2-Aa, Il3, Il4, Il5 (p = 0.026)† |
| Lysosome (12) | Abca2, Atp6v0a2, Gnptab, Ap1g2, Ap3b1, Ap3b2, Ap3d1, Ap4m1, Galns, Lamp2, Manba, Ppt1 (p = 0.032)† |
| Bacterial invasion of epithelial cells (9) | Cd2ap, Rac1, Arhgef26, Was, Wasl, Cdh1, Ilk, Sept11, Sept3 (p = 0.033)† |
| Morphine addiction (10) | Gabra2, Gabrb1, Gabrb3, Gabrg2, Gabrg3, Gnb5, Gng12, Gng2, Gngt2, Slc32a1 (p = 0.034)† |
| Wnt signalling pathway (13) | Crebbp, Rac1, Wif1, Camk2a, Camk2d, Dvl2, Dvl3, Fosl1, Fzd7, Nkd1, Nkd2, Sfrp1, Tbl1xr1 (p = 0.038)† |
| Intestinal immune network for immunoglobin A production (6) | Cd40lg, Cxcl12, H2-Aa, Il4, Il5, Tnfrsf17 (p = 0.049)† |
*
Fisher’s exact test.
†
Significant association (p < 0.05) of differentially expressed genes (Z-score ≥ 1.5) by physical exercise in mice with proteoglycan-induced arthritis was obtained using the DAVID Bioinformatics Resources 6.8 platform (Laboratory of Human Retrovirology and Immunoinformatics, Frederick, Maryland, USA).
GABA, γ-aminobutyric acid; JAK-STAT, Janus kinase-signal transducer and activator of transcription proteins; KEGG, Kyoto Encyclopedia of Genes and Genomes; PGIA, proteoglycan-induced arthritis.