CINC-2 and miR-199a-5p in EVs secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE222517 | GEO | 2023/04/07
REPOSITORIES: GEO
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Project description:Small hepatocyte-like progenitor cells (SHPCs) are hepatocytic progenitor cells that transiently form clusters in rat livers treated with retrorsine and with 70% partial hepatectomy (PH). We previously reported that transplantation of Thy1+ cells derived from D-galactosamine-treated livers promotes SHPC expansion, resulting in the acceleration of liver regeneration. Extracellular vesicles (EVs) produced by Thy1+ cells act on sinusoidal endothelial cells (SECs) and Kupffer cells to secrete IL17B and IL25, respectively, resulting in SHPC activation through IL17 receptor B (RB) signaling. Our aim is to identify factors in Thy1-EVs that activate IL17RB signaling. Thy1+ cells isolated from rats with D-galactosamine-induced liver injury were cultured for one week. Although some liver stem/progenitor cells proliferated into colonies, others maintained as mesenchymal cells (MCs). Thy1-MCs or Thy1-liver stem/progenitor cells were transplanted into retrorsine/PHtreated livers to examine their effects on SHPCs. SHs isolated from adult rat livers were used to validate factors regulating growth induction. The number and size of SHPCs remarkably increased in livers transplanted with Thy1-MCs. Comprehensive analysis of Thy1-MC-EVs revealed that miR-199a-5p, CINC-2, and MCP-1 are candidates for stimulating SHPC growth. Administration of the miR-199a-5p mimic, and not CINC-2, promoted SH growth. SECs treated with CINC-2 induced IL17b expression and their conditioned medium promoted SH growth. Thy1-MC transplantation may accelerate liver regeneration due to SHPCs expansion, which is stimulated by CINC-2/IL17RB signaling and miR-199a-5p.
2023-04-07 | PXD039384 | Pride
Project description:BackgroundSmall hepatocyte-like progenitor cells (SHPCs) are hepatocytic progenitor cells that transiently form clusters in rat livers treated with retrorsine (Ret) that underwent 70% partial hepatectomy (PH). We previously reported that transplantation of Thy1+ cells obtained from D-galactosamine-treated livers promotes SHPC expansion, thereby accelerating liver regeneration. Extracellular vesicles (EVs) secreted by Thy1+ cells induce sinusoidal endothelial cells (SECs) and Kupffer cells (KCs) to secrete IL17B and IL25, respectively, thereby activating SHPCs through IL17 receptor B (RB) signaling. This study aimed to identify the inducers of IL17RB signaling and growth factors for SHPC proliferation in EVs secreted by Thy1+ cells (Thy1-EVs).MethodsThy1+ cells isolated from the livers of rats treated with D-galactosamine were cultured. Although some liver stem/progenitor cells (LSPCs) proliferated to form colonies, others remained as mesenchymal cells (MCs). Thy1-MCs or Thy1-LSPCs were transplanted into Ret/PH-treated livers to examine their effects on SHPCs. EVs were isolated from the conditioned medium (CM) of Thy1-MCs and Thy1-LSPCs. Small hepatocytes (SHs) isolated from adult rat livers were used to identify factors regulating cell growth in Thy1-EVs.ResultsThe size of SHPC clusters transplanted with Thy1-MCs was significantly larger than that of SHPC clusters transplanted with Thy1-LSPCs (p = 0.02). A comprehensive analysis of Thy1-MC-EVs revealed that miR-199a-5p, cytokine-induced neutrophil chemoattractant-2 (CINC-2), and monocyte chemotactic protein 1 (MCP-1) were candidates for promoting SHPC growth. Additionally, miR-199a-5p mimics promoted the growth of SHs (p = 0.02), whereas CINC-2 and MCP-1 did not. SECs treated with CINC-2 induced Il17b expression. KCs treated with Thy1-EVs induced the expression of CINC-2, Il25, and miR-199a-5p. CM derived from SECs treated with CINC-2 accelerated the growth of SHs (p = 0.03). Similarly, CM derived from KCs treated with Thy1-EVs and miR-199a-5p mimics accelerated the growth of SHs (p = 0.007). In addition, although miR-199a-overexpressing EVs could not enhance SHPC proliferation, transplantation of miR-199a-overexpressing Thy1-MCs could promote the expansion of SHPC clusters.ConclusionThy1-MC transplantation may accelerate liver regeneration owing to SHPC expansion, which is induced by CINC-2/IL17RB signaling and miR-199a-5p via SEC and KC activation.
| S-EPMC10190025 | biostudies-literature
Project description:Five-week old male C57BL/6J mice (20 ± 2 g) were intraperitoneally injected with of 20% CCl4 solution in sterile mineral oil at a dose of 2.5 ml CCl4 per kilogram body weight twice per week for eight weeks. Afterwards, the primary hepatocytes were isolated by pronase/collagenase perfusion digestion followed by subsequent density gradient centrifugation. The isolated primary hepatocytes were counted with a hemocytometer to determine the number and percentage of viable cells using the trypan blue method. The isolated cells with the viability above 90% were used for the experiments.
2024-01-01 | GSE243644 | GEO
Project description:In order to gain insight into the effects of aging on susceptibility to environmental toxins, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of male Brown Norway and F344 rats across the adult lifespan. To examine metabolic processes across lifespan after challenge with a xenobiotic compound, Brown Norway rats were exposed to 1.0 g/kg body weight toluene by oral gavage in corn oil (4ml/kg body weight) or corn oil alone. Experiment Overall Design: Brown Norway rats: Analysis of gene expression profiles for XMEs in male Brown Norway rats 4, 12, and 24 months old. Rats were exposed to 1g/kg toluene by oral gavage, and sacrificed after 4 hours. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Rat 230 2.0 full-genome GeneChips. Data from 18 samples, with three rats in each of the control age groups and dosed age groups, were analyzed. Experiment Overall Design: F344 rats: Analysis of gene expression profiles for XMEs in male F344 6, 11, 18, and 24 months old. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Rat 230 2.0 full-genome GeneChips. Data from 16 samples, with four rats in each of the 4 age groups, were analyzed.
2008-10-20 | E-GEOD-11097 | biostudies-arrayexpress
Project description:Male F344 rats were expsoed to sub-toxic (50 or 150 mg/kg) or toxic (1500 or 2000 mg/kg) doses of acetaminophen. RNa was extracted from livers and gene expression analysis was performed on Agilent rat oligonucleotide chips. Keywords: Competitive hybridization
2006-09-19 | GSE5860 | GEO
Project description:Reactivation of fetal gene expression patterns has been demonstrated to play a crucial role in common cardiac diseases in adult life including left ventricular (LV) hypertrophy (LVH). Thus, increased wall stress and neurohumoral activation are discussed to induce the return to expression of fetal genes after birth in LVH. We therefore aimed to test whether fetal gene expression programs are linked to the genetic predisposition to LVH. We performed genome-wide gene expression analysis by microarray-technology in a genetic rat model of LVH, i.e. the stroke-prone spontaneously hypertensive rat (SHRSP), to identify differences in expression patterns between day 20 of development (E20) and week 14 in comparison to a normotensive rat strain with low LV mass, i.e. Fischer (F344). 15232 probes from LV RNA from rats at week 14 and at E20 were detected as expressed (p < 0.05) and screened for differential expression. We identified 24 genes with a SHRSP specific up-regulation and 21 genes up-regulated in F344. Further bioinformatic analysis presented Efcab6, Ephx2 and Kcne1 as candidate genes for LVH that showed only in the hypertensive SHRSP rat a differential expression pattern during development and were significantly differentially expressed in adult SHRSP rats compared with two F344 and normotensive Wistar-Kyoto rats. They represent thus interesting novel targets for further functional analyses and the elucidation of mechanisms leading to LVH. Here we report a new approach to identify candidate genes for cardiac hypertrophy by analysing both gene expression differences between strains with contrasting cardiac phenotype and additionally the gene expression program during development.
2014-07-01 | GSE53512 | GEO
Project description:We analyzed gene expression of hepatocytic parental progenitor cells in a population of small hepatocytes. The hepatocytic parental progenitor cells possess self-renewal capability. These cells maintain the ability to differentiate into mature hepatocytes.
2016-09-08 | GSE86523 | GEO
Project description:To investigate the role of IRF8 in the inflammatory microenvironment of abdominal aortic aneurysm tissue, bone marrow cells were isolated from the tibias and femurs of 8-week-old male mice and cultured with granulocyte-macrophage colony-stimulating factor and Flt3L cytokines to generate CD103-positive dendritic cells. Cells were harvested on days 9 and 15-16 and stimulated with tumor necrosis factor-alpha. Gene ontology analysis revealed upregulation of T cell activation and chemotaxis in bone marrow-derived dendritic cells from IRF8 overexpression mice, indicating IRF8's role in dendritic cell-T cell interactions. Protein-protein interaction analysis highlighted Cd40 and Fcgr1 as key surface markers. IRF8-related genes were enriched in type I interferon signaling pathways, implicating IRF8 in antigen presentation functions of dendritic cells.
2024-10-10 | GSE278890 | GEO
Project description:To investigate the altered patways among sarcomas and MSCs, gene expression profiles were comared among rat osteosarcoma and malignant histiocytoma (MFH) to mesenchymal stem cells (MSCs) from syngeneic origin. Several altered pathways have identified including down-regulation of Wnt, Cell adhesion, ECM interaction and up-regulation of Hedgehog, cell cycling pathways in rat sarcomas compared to MSCs. Gene expression array analysis was perfromed for the samples of rat osteosarcoma COS1NR and malignant fibrous histiocytoma MFH1NR cell lines, bothe established from chemically induced tumors in F344 rats by 4-HAQO, and rat mesenchymal stem cells freshly isolated from femur bone marrow of F344 rats.
2011-10-24 | E-GEOD-33170 | biostudies-arrayexpress
Project description:HIV Tg rats exhibit pulmonary hypertension and pulmonary artery remodeling. In an effort to begin to understand cell signaling pathways which are altered in lungs from HIV transgenic rats, we used microarray analysis. n=3 samples of lung tissue from 3 month old male HIV transgenic rat and n=3 samples of lung tissue from 3 month oldmale F344 (control) rat
2011-08-31 | E-GEOD-27393 | biostudies-arrayexpress