Monocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung.
- Author:
Young Sam LEE
1
;
Jonghoe BYUN
;
Jeong A KIM
;
Jung Sun LEE
;
Koung Li KIM
;
Yeon Lim SUH
;
Jeong Min KIM
;
Hyung Suk JANG
;
Jae Young LEE
;
In Soon SHIN
;
Wonhee SUH
;
Eun Seok JEON
;
Duk Kyung KIM
Author Information
1. Department of Medicine, Cardiac and Vascular Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
connective tissue growth factor;
fibrosis;
hypertrophy;
monocrotaline;
pulmonary hypertension
- MeSH:
Animals;
Blood Pressure/drug effects;
Bronchi/cytology/drug effects/metabolism;
Endothelial Cells/cytology/drug effects/metabolism;
Epithelial Cells/cytology/drug effects/metabolism;
Hypertension, Pulmonary/chemically induced/*metabolism;
Immediate-Early Proteins/genetics/*metabolism;
Intercellular Signaling Peptides and Proteins/genetics/*metabolism;
Lung/cytology/drug effects/*metabolism;
Male;
Monocrotaline/*toxicity;
Pulmonary Alveoli/cytology/drug effects/metabolism;
Pulmonary Artery/cytology/drug effects/metabolism;
Rats;
Rats, Sprague-Dawley;
Research Support, Non-U.S. Gov't;
Reverse Transcriptase Polymerase Chain Reaction;
Up-Regulation
- From:Experimental & Molecular Medicine
2005;37(1):27-35
- CountryRepublic of Korea
- Language:English
-
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 microgram/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.
