Marinobufagenin ( marinobufagin, MBG) is a cardiotonic bufadienolide steroid.[ It is secreted by the toad species such as Bufo marinus.][ It also can be found in the plasma and urine of human subjects with myocardial infarction, kidney failure, heart failure, and preeclampsia.][ MBG is a vasoconstrictor and a sodium–potassium adenosine triphosphatase (Na/K-ATPase) inhibitor with a high affinity for the alpha-1 isoform of the enzyme, the main isoform in the vascular wall and the kidney.][
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It is produced by adrenal cortex and placenta via CYP27a1 pathway.[ MBG regulates the monovalent ions balance and cell homeostasis, and by binding to the Na/K-ATPase, it affects cell growth and differentiation, apoptosis, and proliferation.][ A novel effect of MBG is their ability to induce intracellular signaling, leading to a loss of elasticity and vascular fibrosis.][
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One of the mechanisms of the pro-fibrotic effect of MBG is the inhibition of the activity of Fli1, a nuclear transcription factor and a negative regulator of collagen 1 synthesis. Fli1 competes with another transcription factor, ETS-1, to maintain a balance between stimulation and repression of the collagen-1 gene. The Na/K ATPase/Src/EGFR complex emerges as a signal cascade, which activates phospholipase C, resulting in the phosphorylation of PKCδ and its translocation to the nucleus. In the nucleus, PKCδ phosphorylates Fli1, which withdraws the Fli1-induced inhibition of the collagen-1 promoter and increases procollagen expression and collagen production.[
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The antagonism of the pressor and profibrotic effects of MBG by monoclonal anti-MBG antibodies may lead to the prevention of vascular fibrosis in patients with end-stage renal disease and preeclampsia.[
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