The PI3k/Akt Pathway Is Associated With Angiogenesis, Oxidative Stress and Survival of Mesenchymal Stem Cells in Pathophysiologic Condition in Ischemia

Abstract

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

ELABELA ameliorates hypoxic/ischemic-induced bone mesenchymal stem cell apoptosis via alleviation of mitochondrial dysfunction and activation of PI3K/AKT and ERK1/2 pathways

“…It has been well characterized that the ERK1/2 and PI3K/AKT signaling pathways are critical regulators during the apoptosis process [ 10 , 45 ]. It is important to note the crosstalk between these two signaling axes with mitochondria.…”

“…Apoptosis is generally considered as a vital process to maintain the homeostasis of both tissues and cells, which is regulated by sophisticated apoptotic signals [ 9 ]. A mass of evidence suggests that PI3K/AKT and ERK1/2 signaling pathways are related to cell proliferation and apoptosis [ 10 – 12 ]. Ascending expression of AKT phosphorylation and ERK1/2 phosphorylation seems to be pivotal anti-apoptotic signals [ 13 , 14 ].…”

Modulation of miRNAs by vitamin C in H2O2‑exposed human umbilical vein endothelial cells

“…Research has indicated that all MAPK inhibitors increase the O 2 •- levels in H 2 O 2 -induced A549 cells ( 42 ). The PI3K/Akt signaling pathway is related to survival, angiogenesis and oxidative stress under pathophysiologic conditions in ischemia ( 43 ). Klotho has been shown to weaken oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress in HUVECs via the upregulation of oxidative scavengers by suppressing lectin-like ox-LDL receptor expression and activating the PI3K/Akt/eNOS pathway ( 44 ).…”

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke

“…Also, both 100 Hz and 2 Hz/10 0HZ-EA are effective in improving the recovery of hindlimb motor function in spinal cord injury (SCI) rats; this may be associated with the function of reducing neuronal apoptosis and promoting the autophagy of damaged nerve cells (Luo et al, 2019). The PI3K/AKT pathway plays an important role in regulating cell proliferation, differentiation, migration, and apoptosis in various types of cells (Samakova et al, 2019). Therefore, the PI3K/AKT pathway is a key target for ischemic stroke treatment.…”