Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

28 September 2012

Coexpression of Smad7 and UPA attenuates carbon tetrachloride-induced rat liver fibrosis

Baocan WangABE, Wenxi LiABE, Yingwei ChenC, Yuqin WangD, Chao SunC, Yuanwen ChenD, Hanming LuF, Jiangao FanF, Dingguo LiAF

DOI: 10.12659/MSM.883479

Med Sci Monit 2012; 18(10): BR394-401

Abstract

Background: There is a great need for developing novel therapies to treat liver fibrosis. Previous studies showed that both Smad7 and uPA were inhibitors of liver fibrosis. Therefore, we explored the therapeutic effects of combinational gene therapy with Smad7 and uPA on CCl4-induced liver fibrosis.
Material/Methods: Smad7 and uPA genes were cloned into an adenovirus vector. To observe the therapeutic effects of coexpression of Smad7 and uPA genes, the recombinant adenovirus were delivered into CCL4-induced fibrosis models. Fibrillar collagen, hydroxyproline, α-SMA, TGF-β1, MMP-13, TIMP-1, HGF and PCNA were detected to evaluate the fibrosis and to explore the mechanisms underlying the treatment with Smad7 and uPA.
Results: The results showed that single Smad7 or uPA adenovirus reduced CCL4 induced liver fibrosis significantly; while combination of Smad7 and uPA had more significant therapeutic effect on CCl4 induced liver fibrosis. Then the markers underlying the therapeutic effect of combination of Smad7 and uPA were also explored. Over-expression of Smad7 and uPA inhibited the expression of α-SMA and TGF- β1 significantly. Combinational gene therapy also enhanced extracellular matrix degradation by increasing the expression of MMP-13, inhibiting TIMP-1 expression, and promoted hepatocyte proliferation, while single Smad7 or uPA only induced part of these changes.
Conclusions: These results suggest that combinational gene therapy with Smad7 and uPA inhibited CCl4-induced rat liver fibrosis by simultaneously targeting multiple pathogenic pathways.

Keywords: Recombination, Genetic - genetics, RNA, Messenger - metabolism, Matrix Metalloproteinase 13 - metabolism, Liver Cirrhosis - therapy, Liver - pathology, Hepatocytes - pathology, genetic therapy, Gene Expression Regulation, Enzymologic, Extracellular Matrix - metabolism, Disease Progression, Carbon Tetrachloride, Adenoviridae - genetics, Smad7 Protein - therapeutic use, Tissue Inhibitor of Metalloproteinase-1 - metabolism, Urokinase-Type Plasminogen Activator - therapeutic use

0 Comments

Editorial

01 August 2022 : Editorial  

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937927

Med Sci Monit 2022; 28:e937927

In Press

08 Aug 2022 : Clinical Research  

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Comp...

Med Sci Monit In Press; DOI: 10.12659/MSM.937331  

08 Aug 2022 : Clinical Research  

Hemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Progno...

Med Sci Monit In Press; DOI: 10.12659/MSM.937146  

05 Aug 2022 : Clinical Research  

A Retrospective Study of 98 Elderly Patients with High-Risk Lateral Femoral Wall Intertrochanteric Hip Frac...

Med Sci Monit In Press; DOI: 10.12659/MSM.936923  

04 Aug 2022 : Clinical Research  

Radiological Assessment of Prevalance and Quality of Periapical Status of Endodontic Treatments

Med Sci Monit In Press; DOI: 10.12659/MSM.936569  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750