Project description:Background: Extended hepatectomies may result in post-hepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy. Methods: 40 Wistar rats were subjected to 30%, 70%, or 90% partial hepatectomy, sham operation or no operation. 24 hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Results: Cluster analysis revealed 2 main groupings, one containing the PH(90%) and one containing the remaining groups (baseline, sham, PH(30%) and PH(70%)). Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic functions degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regulators were hepatocyte growth factor and transforming growth factor. Conclusion: With decreasing size of the future liver remnant, the liver tended to prioritize expression of genes involved in cell proliferation and differentiation at the expense of genes involved in metabolism and body homeostasis. This prioritizing may be an essential molecular explanation for post-hepatectomy liver failure.
Project description:Expression of rat hepatocytic progenitor cells with and without hepatic Thy1-positive cells in retrorsine/partial hepatectomy treated rats models.
Project description:miRNA expression was profiled before and during liver regeneration following 2/3 partial hepatectomy (PHx) in chronic ethanol-fed (EtOH) and pair-fed carbohydrate control (CHO) rats. Prior to PHx, EtOH animals were fed a liquid diet containing 36% of the calories from ethanol for 5 weeks. Left lateral and medial (LLM) lobes were removed at time of PHx and used as t = 0 biological controls. Remnant liver tissue (PHx) was harvested 1 h, 6 h, 12 h, and 24 h after PHx. RNA from 4 biological replicates was pooled for profiling miRNA expression on Agilent Rat miRNA Microarrays v1.0. miRNA expression was profiled in the chronic ethanol-fed (EtOH) and carbohydrate control pair-fed (CHO) liver prior to (LLM) and 1 h, 6 h, 12 h, and 24 h after partial hepatectomy (PHx).
Project description:Autonomic nervous system is widely distributed in liver, and some reserchers have found that disruppted autonomic nerves will delay liver regeneration. We used microarrays to further highlight the regulatory role of autonomic nervous system in liver regeneration at gene transcription level. Surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, and the expression profiles of regenerating liver at 2h were detected using Rat Genome 230 2.0 array. Then the significantly changed genes related to liver regeneration (LR)-, injury-, splanchnic nerve-LR-, vagal nerve-LR-, and autonomic nerve-LR-related genes were identified, respectively. The relevance of gene expression profiles and biological processes was analyzed by bioinformatics and systems biology.
Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
Project description:Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. Loss or reduction of KLF6 is linked with progression of experimental and human hepatocellular carcinoma. Despite its important contributions to liver homeostasis and growth, there are no data characterizing the involvement of KLF6 to hepatic regeneration. Microarray data from wildtype and DeltaKlf6 mice were used to identify regulating mechanisms and potential mediators within liver regeneration Wildtype and hepatocyte specific Klf6 knockout mice (DeltaKlf6) were employed for 70% partial liver resection/hepatectomy (PHx) in order to analyse liver regeneration. Twelve hours after partial hepatectomy animals were scrificed and remnant liver tissue was used for further experiemnts. For the overall study we used 6 animals per group, and included RNA from liver tissue of 3 wildtype and 3 DeltaKlf6 animals for the microarray analysis. Wildtype animals were used as controls.