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A single adenovirus-mediated relaxin delivery attenuates established liver fibrosis in rats.

 Ja Kyung Kim  ;  Jung Il Lee  ;  Yong-Han Paik  ;  Chae-Ok Yun  ;  Hye Young Chang  ;  Su Yeon Lee  ;  Kwan Sik Lee 
 JOURNAL OF GENE MEDICINE, Vol.18(1-3) : 16-26, 2016 
Journal Title
Issue Date
Adenoviridae ; Amino Acid Oxidoreductases/metabolism ; Animals ; Collagen/metabolism* ; Extracellular Matrix/metabolism ; Gene Transfer Techniques* ; Genetic Therapy ; Genetic Vectors ; Liver Cirrhosis, Experimental/therapy* ; Male ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Receptors, Peptide/metabolism* ; Relaxin/blood ; Relaxin/genetics* ; Thioacetamide/toxicity ; Tissue Inhibitor of Metalloproteinase-2/metabolism
adenovirus ; liver cirrhosis ; liver fibrinolysis ; liver fibrosis ; lysyl oxidase homolog ; relaxin
BACKGROUND: Liver fibrosis is characterized by an excess accumulation and repressed degradation of extracellular matrix. Although methods of alleviating already established liver fibrosis have scarcely been reported, continuous relaxin (RLX) infusion has demonstrated some promising results. In the present study, we investigated whether a single adenoviral delivery of RLX would attenuate established liver fibrosis in rats.
METHODS: Rats were given thioacetamide (TAA) for 8 weeks and infected once with either RLX-expressing adenovirus (TAA + RLX) or control virus (TAA + Vector) via the tail vein. They were sacrificed either 3 days or 3 weeks after adenovirus infection.
RESULTS: Morphometric analysis of picrosirius red stained area demonstrated that the TAA + RLX group had significantly decreased fibrosis at week 3 when liver fibrosis of the TAA + Vector group remained unchanged. Although the liver and serum RLX levels were elevated on day 3 and reversed by week 3, expression of RLX receptor (Rxfp1; relaxin-like family peptide receptor-1) in TAA + RLX rats was sustained and elevated. The production of tissue cyclic adenosine monophosphate, which is a second messenger of activated Rxfp1, was still enhanced in the TAA + RLX group by week 3. Expression of lysyl oxidase homolog 2, which contributes to collagen cross-linking and is up-regulated by TAA treatment, was significantly decreased by week 3 in the TAA + RLX group. Expression of tissue inhibitor of metalloprotiase-2 was alleviated in the TAA + RLX group at week 3, whereas that of TAA + Vector rats was still elevated.
CONCLUSIONS: A single adenoviral delivery of RLX in the liver attenuated established hepatic fibrosis by suppressing collagen cross-linking and enhancing collagen degradation.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ja Kyung(김자경) ORCID logo https://orcid.org/0000-0001-5025-6846
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Lee, Jung Il(이정일) ORCID logo https://orcid.org/0000-0002-0142-1398
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