First Author | Ye X | Year | 2018 |
Journal | Mol Med Rep | Volume | 18 |
Issue | 4 | Pages | 3611-3618 |
PubMed ID | 30132521 | Mgi Jnum | J:301758 |
Mgi Id | MGI:6506903 | Doi | 10.3892/mmr.2018.9392 |
Citation | Ye X, et al. (2018) Downregulation of Glt25d1 aggravates carbon tetrachlorideinduced acute hepatic injury through activation of the TGFbeta1/Smad2 signaling pathway. Mol Med Rep 18(4):3611-3618 |
abstractText | Collagen beta (1O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via beta (1O) linkages in collagen. The present study investigated the function of the collagen galactosyltransferase activity of GLT25D1 against carbon tetrachloride (CCl4)induced acute liver injury in vitro. Glt25d1+/ mice and wildtype (WT) mice were injected intraperitoneally with the same dose of CCl4. The grade of hepatic injury and the extent of hepatocyte necrosis in the acute phase were assessed 48 h following CCl4 injection. Hepatocyte necrosis was evaluated by histological examination and by serum alanine aminotransferase and aspartate aminotransferase levels, which were higher in the Glt25d1+/ mice compared with those in the WT mice. Reverse transcriptionquantitative polymerase chain reaction was performed, and the results demonstrated that the mRNA expression levels of inflammatory cytokines, including tumor necrosis factoralpha and interleukin6 were significantly increased in the Glt25d1+/ mice. Furthermore, western blot analyses were performed, and the results demonstrated that the protein levels of cleaved caspase3 and 9 were also markedly increased in the Glt25d1+/ liver, indicating that hepatocyte apoptosis was induced. Additionally, the expression levels of transforming growth factor (TGF)beta1 and phosphorylated small mothers against decapentaplegic (Smad)2 were markedly upregulated, indicating activation of the TGFbeta1/Smad2 signaling pathway during CCl4induced acute liver injury in Glt25d1+/ mice. CCl4 administration also resulted in severe damage to Glt25d1+/ primary hepatocytes in vitro. Taken together, the downregulation of Glt25d1 deteriorated CCl4induced liver injury in mice, which may involve triggering inflammatory responses, apoptosis and TGFbeta1/Smad2 signaling pathway activation. |