Expression of p38 mitogen-activated protein kinases, glycogen synthase kinase, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase signaling: Can it be used as molecular markers among trauma-hemorrhagic shock patients?

p38MAPK signaling pathway leads to the multi-organ injury caused by ischemia-reperfusion in animal models. Increased expression of p38MAPK is seen in ischemia-reperfusion models of kidney, liver, vascular and myocardial cells, and lung.[7] Yang et al. showed that in HS rats, MAPK’s signaling pathways indirectly regulate vascular activity.[8] A recent study reported that nuclear factor-kappa B is one of the key players that are involved in the regulation of hypoxic inflammation after HS following resuscitation (H/R).[9,10] McCloskey investigated that the activation of JNK in the liver as an early response to tissue hypoxia soon after the initiation of hemorrhage.[11] A recent study has shown that GSK-3β inhibitor modulates the inflammatory response to stress and may be protective in condition with sepsis inflammation and shock.[12] Multiple signaling pathways including the Akt pathway regulates GSK-3, inactivates it by causing Ser9 phosphorylation. There is a consistent decline in the activation of Akt pathway during the hemorrhage and resuscitation. This indicates an excessive activation of GSK-3β, which leads to both inflammation and tissue injury.[13]