Dataset Information

Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl?-Induced Hepatic Fibrosis Animal Model.

ABSTRACT: Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial?mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl?)-induced hepatic fibrosis in mice. As shown in histological results, CCl? treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl?-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.

SUBMITTER: Gwon MG

PROVIDER: S-EPMC6222866 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl₄-Induced Hepatic Fibrosis Animal Model.

Gwon Mi-Gyeong MG Kim Jung-Yeon JY An Hyun-Jin HJ Kim Woon-Hae WH Gu Hyemin H Kim Min-Kyung MK Park Sok Cheon SC Park Kwan-Kyu KK

Molecules (Basel, Switzerland) 20180810 8

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial⁻mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibroti ...[more]

PMID: 30103395

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Project description:During acute rejection of cardiac transplants endothelial cell-leukocyte interaction fueled by co-stimulatory molecules like CD40/CD154 may ultimately lead to graft loss. One key player in up-regulating the expression of such pro-inflammatory gene products is the interferon-gamma-dependent transcription factor STAT-1. Hence down-regulating interferon-gamma-stimulated pro-inflammatory gene expression in the graft endothelial cells by employing a decoy oligodeoxynucleotide (dODN) neutralising STAT-1 may protect the graft. To verify this hypothesis, heterotopic mouse heart transplantation was performed in the allogeneic B10.A(2R) to C57BL/6 and syngeneic C57BL/6 to C57BL/6 strain combination without immunosuppression. Graft vessels were pre-treated with STAT-1 dODN, mutant control ODN (10 muM each) or vehicle (Ringer solution). Cellular rejection (vascular and interstitial component) was graded histologically and CD40, ICAM-1, VCAM-1, MCP-1, E-selectin and RANTES expression in the graft monitored by real time PCR 24 h and 9 days post-transplantation. Nine days after transplantation both rejection scores were significantly diminished by 85 and 70%, respectively, in STAT-1 dODN-treated allografts as compared to mutant control ODN-treated allografts. According to immunohistochemistry analysis, this was accompanied by a reduced infiltration of monocyte/macrophages and T cells into the graft myocardium. In addition, pro-inflammatory gene expression was strongly impaired by more than 80% in STAT-1 dODN-treated allografts 24 h post-transplantation but not in mutant control ODN or vehicle-treated allografts. This inhibitory effect on pro-inflammatory gene expression was no longer detectable 9 days post-transplantation. Single periprocedural treatment with a STAT-1 dODN thus effectively reduces cellular rejection in mouse heart allografts. This effect is associated both with an early decline in pro-inflammatory gene expression and a later drop in mononuclear cell infiltration.

Dataset Information

Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl?-Induced Hepatic Fibrosis Animal Model.

Publications

Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl₄-Induced Hepatic Fibrosis Animal Model.

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