FK 409 Ameliorates Small-for-Size Liver Graft Injury by Attenuation of Portal Hypertension and Down-Regulation of Egr-1 Pathway

Abstract

Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.

The Protective Effects of <i>N</i>-n-butyl Haloperidol Iodide on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Egr-1 Overexpression

“…Combining with the literature, it is reasonable to speculate that the anti-inflammatory effect of F 2 is associated with its inhibition of the expression of Egr-1 and the secretion of TNF-α. TNF-α is an important downstream inflammatory gene of Egr-1 [16,24], and it can in turn activate inflammatory cells such as neutrophil which can result in the increase of MPO activity. Based on these findings, it seems reasonable to speculate that the cardioprotective activity of F 2 in myocardial I/R might be associated with blocking Egr-1 expression/TNF-α secretion/neutrophil activation/ MPO release pathway.…”

“…Basing on results of a model of lung I/R, Yan et al proposed that Egr-1 could be a master switch to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability which are thought to be the central pathogenesis of I/R injury [11]. Likewise, other studies have reported that drugs targeting the Egr-1 could prevent hepatic I/R injury by inhibiting expression of Egr-1 [15,16]. These findings indicate that the overexpression of Egr-1 could be the common denominator in I/R injury in various organs and Egr-1 might be a good therapeutic target in the I/R conditions.…”

Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal

“…Indeed, both intramammary pressure (43) and mammary blood flow (16) are responsive to milk removal, and changes in expression of genes associated with mammary inflammation are known to be associated with 4ϫ milking (12), once daily milking (33), and milk stasis (45). In addition, expression of EGR-1 is co-regulated with acute-phase response genes during inflammation in the eye (15), liver (36), and lung (39). Moreover, EGR-1 expression is upregulated as part of the mammary response to milk accumulation (53), and it is also upregulated and thought to mediate immediate early changes in blood flow during liver remodeling (41).…”

Small‐for‐Size Syndrome After Partial Liver Transplantation: Definition, Mechanisms of Disease and Clinical Implications

“…As detailed above, most available clinical trials have focused on reduction of portal venous pressure and flow. Three studies in rats have targeted vascular regulation in partial grafts: treatment with the nitric oxide donor FK409 was able to ameliorate graft injury (39), while an endothelin-receptor-A antagonist had effects on microcirculation, biochemistry and histology, but did not improve survival (40). Treatment with prostaglandin E1 improved survival in partial steatotic grafts in rats (13).…”