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Temporal alterations in specific basement membrane components in lungs from monocrotaline-treated rats
D W Lipke1, S S Arcot, M N Gillespie
1Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
American Journal of Respiratory Cell and Molecular Biology
|October 1, 1993
Summary
Monocrotaline-induced pulmonary hypertension in rats shows increased basement membrane components like fibronectin and laminin in lung vasculature and parenchyma. These changes suggest a role in the disease
Area of Science:
- Pulmonary Hypertension Research
- Extracellular Matrix Biology
- Animal Models of Disease
Background:
- Pulmonary hypertension (PH) is a severe condition characterized by high blood pressure in the pulmonary arteries.
- The monocrotaline (MCT) model in rats is a widely used experimental system to study PH.
- Basement membrane (BM) components are crucial for tissue structure and function, and their alterations may contribute to PH pathogenesis.
Purpose of the Study:
- To investigate the temporal changes in messenger RNA (mRNA) and protein deposition of basement membrane components in the lungs during the development of MCT-induced pulmonary hypertension.
- To correlate these molecular changes with the established physiological and structural hallmarks of PH in the rat model.
Main Methods:
- Rats were administered a single subcutaneous dose of monocrotaline (MCT).
- Northern blot analysis was used to quantify mRNA levels of various BM components (laminin, perlecan, type IV collagen, fibronectin).
- Immunohistochemistry was employed to assess the protein deposition of these BM components in lung tissue at different time points post-MCT administration.
Main Results:
- MCT administration induced sustained increases in lung and right ventricular mass, and pulmonary arterial pressure.
- Early increases in mRNA for laminin, perlecan, and fibronectin were observed, with fibronectin mRNA remaining elevated throughout the study.
- Increased deposition of fibronectin, laminin, perlecan, type IV collagen, and BM-chondroitin sulfate proteoglycan was detected in the pulmonary vasculature and lung parenchyma over time.
Conclusions:
- The study demonstrates significant temporal alterations in basement membrane component mRNA and protein levels during MCT-induced pulmonary hypertension.
- Accumulation of specific BM components in the pulmonary vasculature and parenchyma appears to be a key feature of this PH model.
- These findings suggest that basement membrane remodeling contributes to the pathogenesis and maintenance of hypertensive pulmonary vascular disease.