title: Monocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung.
abstract: Pulmonary hypertension (PH) is characterized by structural and functional changes in the lung including proliferation of vascular smooth muscle cells (VSMCs) and excessive collagen synthesis. Although connective tissue growth factor (CTGF) is known to promote cell proliferation, migration, adhesion, and extracellular matrix production in various tissues, studies on the role of CTGF in pulmonary hypertension have been limited. Here, we examined CTGF expression in the lung tissues of male Sprague Dawley rats treated with monocrotaline (MCT, 60 microg/kg), a pneumotoxic agent known to induce PH in animals. Establishment of PH was verified by the significantly increased right ventricular systolic pressure and right ventricle/left ventricle weight ratio in the MCT-treated rats. Histological examination of the lung revealed profound muscular hypertrophy in the media of pulmonary artery and arterioles in MCT-treated group. Lung parenchyma, vein, and bronchiole did not appear to be affected. RT-PCR analysis of the lung tissue at 5 weeks indicated significantly increased expression of CTGF in the MCT-treated group. In situ hybridization studies also confirmed abundant CTGF mRNA expression in VSMCs of the arteries and arterioles, clustered pneumocytes, and infiltrated macrophages. Interestingly, CTGF mRNA was not detected in VSMCs of vein or bronchiole. In saline-injected control, basal expression of CTGF was seen in bronchial epithelial cells, alveolar lining cells, and endothelial cells. Taken together, our results suggest that CTGF upregulation in arterial VSMC of the lung might be important in the pathogenesis of pulmonary hypertension. Antagonizing the role of CTGF could thus be one of the potential approaches for the treatment of PH.
authors.affiliation: Department of Medicine, Cardiac and Vascular Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Lee
authors.forename: Jonghoe
authors.initials: J
authors.lastname: Byun
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Koung Li
authors.initials: KL
authors.lastname: Kim
authors.forename: Yeon-Lim
authors.initials: YL
authors.lastname: Suh
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyung-Suk
authors.initials: HS
authors.lastname: Jang
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: In-Soon
authors.initials: IS
authors.lastname: Shin
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D016686:Monocrotaline