Transplantation of Thy1(+) Cells Accelerates Liver Regeneration by Enhancing the Growth of Small Hepatocyte-Like Progenitor Cells via IL17RB Signaling
STEM CELLS
Authors: Ichinohe, Norihisa; Ishii, Masayuki; Tanimizu, Naoki; Kon, Junko; Yoshioka, Yusuke; Ochiya, Takahiro; Mizuguchi, Toru; Hirata, Koichi; Mitaka, Toshihiro
Abstract
Small hepatocyte-like progenitor cells (SHPCs) transiently form clusters in rat livers treated with retrorsine (Ret)/ 70% partial hepatectomy (PH). When Thy1(+) cells isolated from D-galactosamine-treated rat livers were transplanted into the livers of Ret/ PH-treated rats, the mass of the recipient liver transiently increased during the first 30 days after transplantation, suggesting that liver regeneration was enhanced. Here we addressed how Thy1(+) cell transplantation stimulates liver regeneration. We found that the number and size of SHPC clusters increased in the liver at 14 days after transplantation. GeneChip analysis revealed that interleukin 17 receptor b (IL17rb) expression significantly increased in SHPCs from livers transplanted with Thy1(+) cells. We subsequently searched for ligand-expressing cells and found that sinusoidal endothelial cells (SECs) and Kupffer cells expressed Il17b and Il25, respectively. Moreover, extracellular vesicles (EVs) separated from the conditioned medium of Thy1(+) cell culture induced IL17b and IL25 expression in SECs and Kupffer cells, respectively. Furthermore, EVs enhanced IL17rb expression in small hepatocytes (SHs), which are hepatocytic progenitor cells; in culture, IL17B stimulated the growth of SHs. These results suggest that Thy1-EVs coordinate IL17RB signaling to enhance liver regeneration by targeting SECs, Kupffer cells, and SHPCs. Indeed, the administration of Thy1-EVs increased the number and size of SHPC clusters in Ret/ PH-treated rat livers. Sixty days post-transplantation, most expanded SHPCs entered cellular senescence, and the enlarged liver returned to its normal size. In conclusion, Thy1(+) cell transplantation enhanced liver regeneration by promoting the proliferation of intrinsic hepatic progenitor cells via IL17RB signaling.
mRNA expression of interleukins and Th1/Th2 imbalance in patients with pulmonary embolism
MOLECULAR MEDICINE REPORTS
Authors: Duan, Qianglin; Lv, Wei; Wang, Lemin; Gong, Zhu; Wang, Qiang; Song, Haoming; Wang, Hao
Abstract
Few studies have investigated the changes of Th1- and Th2-type cytokines in pulmonary embolism (PE) patients. In this study, the gene expression of interleukins and the balance of Th1- and Th2-type cytokines in the peripheral blood mononuclear cells (PBMCs) of PE patients and controls were investigated. A total of 20 PE patients and 20 gender-and age-matched controls were included in the study. Human cDNA microarray analysis was used to detect the differences in cytokine gene expression between the two groups and a random variance model corrected t-test was used to analyze the statistical data. In comparison with the controls, 12 genes were found to be downregulated, specifically. IL1A, IL9, IL17B, IL19, IL23A, IL25 (P<0.05), IL2, IL3, IL13, IL22, IL24 and IL31 (P<0.01), and 2 genes were found to be upregulated, specifically IL10 and IL28A, in the PE patients. The expression levels of IFN-gamma and IL2 mRNA in the PE patients were significantly lower than those in the control group (P<0.01), while the IL20 mRNA expression levels were significantly upregulated (P<0.01). We conclude that there are significant differences in interleukin gene expression between the PE patients and the control group. A shift of the Th1/Th2 balance comprising enhanced Th2 activity and reduced Th1 activity in the PE patients is also demonstrated.