{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T03:07:30Z","timestamp":1772593650003,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T00:00:00Z","timestamp":1467244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ministry of Health & Welfare, Republic of Korea","award":["HI15C2364"],"award-info":[{"award-number":["HI15C2364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Bone marrow-derived mesenchymal stem cells (BM-MSCs) are known to have an antifibrotic effect and could be used as vehicles for targeted gene delivery. Decorin plays a protective role against fibrogenesis by modulating the degradation of the extracellular matrix. The aim of this study was to determine whether the antifibrotic effect of a combination treatment consisting of BM-MSCs and decorin on hepatic fibrosis is superior to BM-MSCs alone. The effects of BM-MSCs infected with decorin-expressing adenovirus (DCN-MSCs) on hepatic fibrosis were examined in a rat model of thioacetamide (TAA)-induced cirrhosis. The effects of infection with decorin-expressing adenovirus and of incubation with the conditioned medium of DCN-MSCs on transforming growth factor-\u03b2 (TGF-\u03b2) signaling were analyzed in immortalized human hepatic stellate cells (HSCs). According to the Laennec fibrosis scoring system, cirrhotic livers from rats treated with DCN-MSCs exhibited histological improvement compared with cirrhotic livers from rats treated with control adenovirus-infected MSCs (CA-MSCs). DCN-MSC treatment reduced hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with DCN-MSCs than with CA-MSCs. The upregulation of collagen-1, \u03b1-smooth muscle actin (\u03b1-SMA), TGF-\u03b21, and Smad3 phosphorylation in cirrhotic livers was prevented by DCN-MSC administration. Intriguingly, medium from cultured DCN-MSCs blocked both Smad3 phosphorylation and exogenous TGF-\u03b21 stimulated \u03b1-SMA synthesis in HSCs. DCN-MSCs exert strong protective effects against hepatic fibrosis by suppressing TGF-\u03b2\/Smad signaling. Thus, treatment with DCN-MSCs is a potentially novel and efficient therapeutic approach for patients with intractable cirrhosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Furthermore, the significant inhibitory effect of BM-MSCs infected with decorin-expressing adenovirus was attributed to suppressing transforming growth factor-\u03b2 (TGF-\u03b2)\/Smad signaling pathway, supported by attenuation of TGF-\u03b21 expression and inhibition of Smad3 phosphorylation. Therefore, treatment with BM-MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.5966\/sctm.2015-0323","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T02:54:11Z","timestamp":1467341651000},"page":"1247-1256","source":"Crossref","is-referenced-by-count":47,"title":["Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis"],"prefix":"10.1093","volume":"5","author":[{"given":"Yoon Ok","family":"Jang","sequence":"first","affiliation":[{"name":"a \u00a0Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"},{"name":"b \u00a0Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mee-Yon","family":"Cho","sequence":"additional","affiliation":[{"name":"c \u00a0Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chae-Ok","family":"Yun","sequence":"additional","affiliation":[{"name":"d \u00a0Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soon Koo","family":"Baik","sequence":"additional","affiliation":[{"name":"a \u00a0Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"},{"name":"b \u00a0Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu-Sang","family":"Park","sequence":"additional","affiliation":[{"name":"e \u00a0Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Kuy","family":"Cha","sequence":"additional","affiliation":[{"name":"e \u00a0Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sei Jin","family":"Chang","sequence":"additional","affiliation":[{"name":"f \u00a0Department of Preventive Medicine and Institute of Occupational Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moon Young","family":"Kim","sequence":"additional","affiliation":[{"name":"a \u00a0Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoo Li","family":"Lim","sequence":"additional","affiliation":[{"name":"a \u00a0Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Ok","family":"Kwon","sequence":"additional","affiliation":[{"name":"a \u00a0Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,6,30]]},"reference":[{"key":"2021122705044725300_R1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"issue":"suppl 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