Table 1.
Annotated list of genes upregulated in TKA with tourniquet
| Gene | P adj | Pathway/Function |
|---|---|---|
| Cell stess‐‐MAPK | ||
| FOSL2 | 1.68E‐06 | Transcriptio factor activated by MAPK, oxidative stress |
| CEBPD | 0.0116525 | bZIP transcriptio factor involved in inflammation; apoptosis |
| CYR61 | 0.0125334 | ECM protein involved in integrin binding; MAPK, FAK, paxillin, and Rac signaling |
| GADD45B | 0.0157925 | p38/JNK, MAPK inducible; apoptosis |
| GPR4 | 0.0262557 | G‐protein coupled receptor; PTX sensitive; interacts with p38 MAPK |
| MAP3K8 | 0.030141 | Stress activated; activates fos and jun |
| DUSP5 | 0.0427241 | Negative regulator of MAPK |
| Cell stress‐‐JNK | ||
| PIM1 | 1.36E‐05 | Ser/thr kinase that binds STAT3/STAT5 |
| CXCL2 | 0.0001392 | Chemokine induced by NFkB and JNK |
| CCL2 | 0.0157925 | NFkB inducible chemokine; chemotactic for monocytes, basophils |
| GADD45B | 0.0157925 | p38/JNK, MAPK inducible; apoptosis |
| CXCL1 | 0.0181886 | Oxidative stress‐inducible cytokine |
| PIM1 | 1.36E‐05 | Ser/thr kinase that binds STAT3/STAT5 |
| Cell stress‐‐JAK‐STAT | ||
| PIM1 | 1.36E‐05 | Ser/thr kinase that binds STAT3/STAT5 |
| CEBPD | 0.0116525 | bZIP transcription factor induces inflammation; apoptosis |
| CISH | 0.0173316 | SH2‐domain protein; STAT inhibition, cytokine‐inducible negative regulators of cytokine signaling |
| SOCS3 | 0.0181886 | Negative regulation of cytokine signaling; STAT inhibition |
| Cell stress‐‐NFkB | ||
| CXCL2 | 0.0001392 | NFkB inducible chemokine |
| BCL3 | 0.009318 | B cell proto‐oncogene and transcription factor that interacts with NFkB, fos, jun |
| CCL2 | 0.0157925 | NFkB inducible; chemotactic for monocytes, basophils |
| FRMD8 | 0.0157925 | FERM domain containing cytoskeletal protein, interacts with iKB |
| MT1A | 0.015942 | Metalotheionein involved in zinc metalation of carbonic anhydrase |
| CXCL1 | 0.0181886 | Oxidative stress inducible chemokine |
| NFKBIZ | 0.0182906 | Inhibitor of NFkB |
| HES1 | 0.019757 | bHLH transcription factor that interacts with sirtuin |
| GPR56 | 0.0198688 | G‐protein coupled receptor that interacts with NFkB, mTOR |
| TNFRSF1A | 0.029797 | TNF receptor, activates NFkB, anti‐apoptotic proteins BCL‐2 interacting |
| PTX3 | 0.0380791 | Complement‐dependent inflammation; activated by NFkB, jun, fos |
| Cell stress‐‐Akt | ||
| NEDD9 | 0.018291 | Crk‐associated substrate family protein that interacts with T cell receptor interaction; Integrin to Akt signaling |
| NFIL3 | 0.018789 | Transciption factor that regulates IL3 transcription |
| RGS16 | 0.0220731 | Regulator of G protein signaling; blocks mTOR,PIP3, Akt autophagy suppression |
| Cell stress‐‐p53 | ||
| GADD45B | 0.015792 | p38/JNK, MAPK inducible; apoptosis |
| KDM6B | 0.015792 | Lysine‐specific histone demethylase that regulates Wnt signaling |
| PLK3 | 0.0181886 | Polo‐like kinase that interacts with p53; cell cycle |
| CDKN1A | 0.0181886 | Cyclin‐dependent kinase inhibitor controlled by p53 |
| SIPA1L1 | 0.0377431 | p53 degration |
| Cell cycle | ||
| ETS2 | 0.0157925 | ETS transcription factor interacts with c‐jun, CDK10 |
| MYC | 0.0279383 | Nuclear protein; cell cycle, apoptosis, cell transformation |
| Cholesterol regulation | ||
| CH25H | 0.0064543 | Cholesterol hydroxylase cleaves cholesterol in ER; IFN inducible |
| LDLR | 0.0157925 | Mediates endocytosis of LDL |
| Complement and coagulation | ||
| HBB | 0.0181886 | Interacts with hemoglobin, alpha 1 |
| SERPINE1 | 0.0194836 | Serine protease that regulates fibrinolysis |
| PTX3 | 0.0380791 | Complement‐dependent inflammation; activated by NFkB, jun, fos |
| Early response genes | ||
| APOLD1 | 0.0157925 | Early response endothelial apolipoprotein |
| ZFP36L1 | 0.0181886 | Early response gene; zinf finger transcription factor |
| Glucose regulation | ||
| SLC2A3 | 5.548E‐05 | Glucose transporter involved in glucose regulation |
| PFKFB3 | 0.0004144 | Glucose regulation, regulates CDK, cell cycle |
| Hypoxia/Oxidative stress inducible | ||
| FOSL2 | 1.68E‐06 | Transcription factor involved in MAPK |
| MAFF | 0.0055774 | bZIP transcription factor; binds NRF2 transcription factor for nuclear transport, competes with FOS for antioxidant response element binding |
| MT1X | 0.0095178 | Metallothionein |
| MT2A | 0.0157925 | Metallothionein; interacts with PD1 |
| CXCL1 | 0.0181886 | Oxidative stress inducible cytokine |
| MAT2A | 0.0181886 | Hypoxia‐induced, HIF‐dependent methionine adenosyltransferase II, alpha |
| RASD1 | 0.0220731 | Oxidative stress inducible small GTPase involved in iron uptake regulation |
| PDE4B | 0.0256044 | Hypoxia inducible cAMP specific phosphodiesterase |
| MAP3K8 | 0.030141 | Stress‐activated kinase; activates fos and jun |
| TIPARP | 0.0370331 | Oxidative stress inducible poly(ADP‐ribose) polymerase |
| CHAC1 | 0.0392172 | Oxidative stress; degrades glutathione, apoptosis‐related transcription factors regulate |
| Immune cell regulation | ||
| EGR3 | 0.0093178 | Transcription factor that controls B and T cell proliferation |
| ZC3H12A | 0.0157925 | RNase involved in immune response, Toll‐like receptor responsive; mRNA decay |
| NEDD9 | 0.0182906 | Crk‐associated substrate family; T cell receptor interaction; Integrin to Akt signaling |
| MMP19 | 0.0220731 | Metalloproteinase; Th cells surface marker |
| CD83 | 0.0297967 | T cell activation |
| TNFRSF1A | 0.0297967 | TNF receptor, activates NFkB, anti‐apoptotic proteins BCL‐2 interacting |
| SERPINB9 | 0.0440829 | Serine protease inhibitor protects mast cells against apoptosis |
| Wnt signaling | ||
| CSRNP1 | 0.0116525 | Nuclear protein induced by axin1 (Wnt); induces apoptosis |
| KDM6B | 0.0157925 | Lysine‐specific histone demethylase that regulates Wnt signaling |
| GJA1 | 0.0181886 | Gap junction protein that regulates cell communication; connexin; Wnt target gene |