The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells

Abstract

By gating the traffic of molecules and cells across the vessel wall, endothelial cells play a central role in regulating cardiovascular functions and systemic homeostasis and in modulating pathophysiological processes such as inflammation and immunity. Accordingly, the loss of endothelial cell integrity is associated with pathological disorders that include atherosclerosis and cancer. The p38 mitogen-activated protein kinase (MAPK) cascades are major signaling pathways that regulate several functions of endothelial cells in response to exogenous and endogenous stimuli including growth factors, stress and cytokines. The p38 MAPK family contains four isoforms p38α, p38β, p38γ and p38δ that are encoded by four different genes. They are all widely expressed although to different levels in almost all human tissues. p38α/MAPK14, that is ubiquitously expressed is the prototype member of the family and is referred here as p38. It regulates the production of inflammatory mediators, and controls cell proliferation, differentiation, migration and survival. Its activation in endothelial cells leads to actin remodeling, angiogenesis, DNA damage response and thereby has major impact on cardiovascular homeostasis, and on cancer progression. In this manuscript, we review the biology of p38 in regulating endothelial functions especially in response to oxidative stress and during the metastatic process.

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

“…34,35 Deregulation of JNK and p38MAPK is associated with various human diseases, including IHD. 34,35 Deregulation of JNK and p38MAPK is associated with various human diseases, including IHD.…”

Focal adhesion kinase, RhoA, and p38 mitogen‐activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors

“…p38MAPK can participate in either proapoptotic or proliferative processes depending on the specific p38MAPK isoform, the cell type and the signaling mechanism involved . It has been described that the Rho small GTPases family activates p38MAPKs . The ability of p38MAPK to phosphorylate caspases constitutes a survival signal as shown in isolated human granulocytes .…”

“…The family of Rho GTPases has been identified as upstream activator of the p38MAPK pathway. 36 The proapoptotic or prosurvival role of p38MAPK depends on the specific isoform activated, cell type and the participating signaling mechanism, as review recently. 37 To evaluate the possible participation of p38MAPK in the signaling mechanism, we studied the effect of SB203580, a specific p38MAPK inhibitor, on apoptosis induced by Ang II.…”

New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs

“…Activation of EphB4 upon interaction with ephrinB2 may promote EC–EC repulsion, which is crucial for angiogenesis and vascular development. Recent studies disclosed several key signaling pathways regulating angiogenesis . These emerging signaling factors provide new targets for the discovery of antiangiogenic agents.…”

“…Recent studies disclosed several key signaling pathways regulating angiogenesis. [13][14][15] These emerging signaling factors provide new targets for the discovery of antiangiogenic agents.…”