microRNAs are conserved, small non-coding RNAs that negatively regulate expression of messenger RNAs at the post-transcriptional level. miRNAs have been found to be differentially expressed in cardiac remodeling and ischemia reperfusion injury. They are also reported to be central players in anti- and profibrotic gene regulation during liver fibrosis. Associations between circulating microRNAs and non-alcoholic fatty liver has been documented.miR21 and miR155 were found to be significantly up regulated in mice fed with a choline deficient and amino acid deficient diet which developed NASH and hepatocellular carcinoma.miR21 has been found to target grainyhead-like3, causing its repression and this can leading to dephosphorylation of Gentamycin Sulfate endothelial nitric oxide synthase, a crucial mediator of endothelial function. Based on the above literature N6022 reports, we hypothesized that adipokine leptin mediates endothelial dysfunction; inflammation and fibrosis through upregulation of miR21 and repression of target Grhl3. To study the mechanisms underlying the leptin-miR21 axis we used toxin-induced experimental NASH models which included oxidative stress as a second hit in an underlying condition of obesity and insulin resistance. The results showed that leptin and leptin signaling through its receptor up regulates miR21 in NASH livers. The upregulation of miR21 strongly correlated to depletion of Grhl3, decrease in NOS3 phosphorylation and increase in the protein levels of sinusoidal endothelial dysfunction markers, while leptin knockout, leptin receptor knockout or miR21 knockout mice did not show any of the described effects. We also validated our results in an accepted model of steatohepatitis and fibrosis Methionine-Choline deficient diet that does not have an underlying condition of obesity. Malignant melanomas originate from the oncogenic transformation of melanocytes the pigment cells of the skin and the eyes. These among others stem from a multipotent neural crest stem cell that expresses the nerve growth factor receptor CD271 and the SRY-box transcription factor SOX10.