RPC1063 Another study collected serum samples from BA

Another study collected serum samples from BA and non-BA neonatal cholestasis and performed microarray analysis that identified 13 differentially expressed miRNAs. The authors performed qRT-PCR on 8 miRNAs that had been previously identified as differentially expressed in BA versus non-BA samples (first sentence) and from these 8 miRNAs that they analyzed they verified that the miRNAs referenced in the sentence were either up or down regulated. No significant change in RPC1063 was noted in the other analyzed miRNAs. Functional enrichment analysis showed that miR-4689 and miR-4429 targeted genes were involved in the forkhead box O (FOXO)3 signaling pathway. Furthermore, area under the curve analysis showed that miR-4689 and miR-4429 had the potential to be useful biomarkers. Considering BA is associated with enhanced biliary inflammation, it is important to recognize the role that miRNAs may play during the inflammatory process. One study looked at the role that miR-124 and miR-200 play during interleukin(IL)-6/signal transducer and activator of transcription (STAT)3 signaling. IL-6 has been recognized as a key regulator of cholangiocyte proliferation. miRNA analyses revealed 84 miRNAs that were decreased and 169 miRNAs that were increased in liver samples from BA patients compared with controls. Out of these miRNAs, miR-124 expression was decreased approximately 5-fold and members of the miR-200 family were increased approximately 5- to 10-fold. These results were confirmed by qRT-PCR. Moreover, expression of miR-124 was inversely correlated with STAT3, and expression of miR-200a inversely correlated with forkhead box (FOX)A2. Binding efficiency between these miRNAs and their respective mRNAs were predicted by TargetScan analysis and confirmed by luciferase assay. In continuing study of other members of the miR-200 family, a second report found that BA patients had increased hepatic miR-200b expression that positively correlated with the degree of hepatic fibrosis. Furthermore, in vitro studies indicated that miR-200b increased human hepatic stellate cell proliferation, migration and fibrotic reaction through modulation of PI3K/AKT signaling and matrix metalloproteinase 2 expression. Combined, these studies allude to the diagnostic value of hepatic expression of miR-200 family members and further suggest that therapeutic intervention of these miRNAs may play a role in fibrotic progression.
Polycystic liver disease Polycystic liver disease (PLD) refers to a group of rare, inherited disorders in which structural changes in the biliary tree cause multiple cholangiocyte-derived cysts to develop within the liver. The most common complications associated with PLD include hypertension, back pain, abdominal distension, dyspnea, gastroesophageal reflux, cyst hemorrhage and infection. PLD can occur on its own (autosomal dominant polycystic liver disease [ADPLD]) or develop as a consequence of autosomal dominant polycystic kidney disease (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). These three PLD-causing diseases arise from different inherited genetic mutations; development of ADPLD is due to mutations in protein kinase C substrate 80K-H (PRKCSH) and/or translocation protein SEC63 homolog (SEC63) genes; ADPKD is caused by mutations in the polycystin-1 and -2 (PKD-1 and PKD-2) genes; and ARPKD is due to mutations in the polycystic kidney and hepatic disease-1 (PKHD-1) gene. Further perturbation of PLD occurs by malformation of the ductal plate and abnormal cell signaling and function. Currently, therapeutic intervention relies heavily on the use of somatostatin analogs, and while these treatments tend to significantly decrease liver volume, there is only a slight improvement in symptoms. Surgical procedures, such as fenestration of cysts and liver resection, tend to significantly relieve symptoms but have a high recurrence rate of cyst formation and symptoms. Very limited information exists regarding miRNA initiation, regulation, or expression during PLD.