Change in the cells that express connective tissue growth factor in acute Coxsackievirus-induced myocardial fibrosis in mouse.
Cardiac fibrosis and inflammation are major pathologic conditions that result from viral myocarditis. Connective tissue growth factor (CTGF) stimulates fibroblast proliferation and induces production of extracellular matrix molecules. We studied the correlation between CTGF and cardiac fibrosis in an acute Coxsackievirus B3 (CVB3) myocarditis animal model. Eight-week-old BALB/c mice were infected intraperitoneally with 10(4) plaque forming units (PFU) of CVB3. Myocardial inflammation peaked on day 7 and decreased markedly by day 14 post-infection (pi); cardiac fibrosis was noted from day 7 and peaked on day 14. By contrast, CTGF was weakly expressed by the interstitial cells in uninfected control hearts and also in the hearts of day 3 pi. CTGF expression measured by real-time PCR was elevated on day 3 and peaked on day 7 pi. TGF-beta expression peaked at day 7 pi. The cell type of CTGF expression changed from interstitial cells to myocytes after virus infection. On day 7, CTGF was strongly expressed by myocytes and inflammatory cells surrounding calcified necrotic areas. In addition, cardiac myocytes expressed CTGF on day 14. Our results, based on an acute CVB3 model of myocarditis, provide evidence that CTGF may mediate the development of fibrosis after viral myocarditis, and that the cells expressed CTGF changes during the course of viral myocarditis.
Yun
Soo-Hyeon
SH
Department of Medicine, Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, 50 Il-won Dong, Kangnam-Ku, Seoul 135-710, South Korea.
Shin
Jae-Ok
JO
Lim
Byung-Kwan
BK
Kim
Kyoung-Li
KL
Gil
Chae-Ok
CO
Kim
Duk-Kyung
DK
Jeon
Eun-Seok
ES
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D024042:Collagen Type I / Q000235:genetics; D055513:Connective Tissue Growth Factor; D003384:Coxsackievirus Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics
C526318:CCN2 protein, mouse; D024042:Collagen Type I; D017931:DNA Primers; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor