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CINC-2 and miR-199a-5p in EVs secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration

ABSTRACT: Thy1 + cells isolated from male F344 rats with Dgalactosamine-induced liver injury were cultured for one week. Bone marrow mesenchymal cells isolated from from the femurs and tibias of a 5-week old male F344 rat. Small hepatocytes (SH) and mature hepatocytes (MH) were isolated from normal livers of 7-week old male F344 rat, Extracellular vesicles (EVs) were separedt from culture media by ultracentrifugation.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE222517 | GEO | 2023/04/07

REPOSITORIES: GEO

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CINC-2 and miR-199a-5p in exosomes secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration

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.

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Transcription profiling of male rats Brown Norway and F344 reveals coordinated changes in xenobiotic metabolizing enzyme gene expression in aging

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