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Identification of the molecular targets of Orm1 in regenerating mouse liver

ABSTRACT: To identify the molecular targets of orosomucoid (Orm1) during liver regeneration, GeneChip analysis was performed at 48 h after partial hepatectomy (PH) in regenerating mouse liver treated with siControl or siOrm. A total of 180 differentially expressed genes in Orm1 konckdown mouse liver by comparing with siControl were identified with a fold change more than 2. Then, pathway analysis performed on the altered gene expression profiles using Ingenuity Pathways Analysis (IPA) program revealed that cell cycle, Toll-like receptor and TGF-beta receptor signaling pathways were under control of Orm1 in regenerating mouse livers.

ORGANISM(S): Mus musculus

PROVIDER: GSE83733 | GEO | 2016/07/01

SECONDARY ACCESSION(S): PRJNA327314

REPOSITORIES: GEO

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Project description:Normal adult liver is uniquely capable of renewal; and repair after injury. Whether this response; represents simple hyperplasia of various liver elements; or requires recapitulation of the genetic program of; the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferationassociated genes. Consistent with these findings, realtime polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level, restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury. Experiment Overall Design: In order to elucidate the molecular similarities between regenerating and developing liver, we performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for targets at 0, 1, 2, 6, 12, 18, 24, 30, 48, and 72 hours after partial hepatectomy and at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc). Experiment Overall Design: Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.

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Identification of the molecular targets of Orm1 in regenerating mouse liver

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