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Role of extracellular matrix and its regulators in human airway smooth muscle biology.
Cell Biochem Biophys. 2006; 44(1):139-46.CB

Abstract

Altered extracellular matrix (ECM) deposition contributing to airway wall remodeling is an important feature of asthma and chronic obstructive pulmonary disease (COPD). The molecular mechanisms of this process are poorly understood. One of the key pathological features of these diseases is thickening of airway walls. This thickening is largely to the result of airway smooth muscle (ASM) cell hyperplasia and hypertrophy as well as increased deposition of ECM proteins such as collagens, elastin, laminin, and proteoglycans around the smooth muscle. Many growth factors and cytokines, including fibroblast growth factor (FGF)-1, FGF-2, and transforming growth factor (TGF)-beta1, that are released from the airway wall have the potential to contribute to airway remodeling, revealed by enhanced ASM proliferation and increased ECM protein deposition. TGF-beta1 and FGF-1 stimulate mRNA expression of collagen I and III in ASM cells, suggesting their role in the deposition of extracellular matrix proteins by ASM cells in the airways of patients with chronic lung diseases. Focus is now on the bidirectional relationship between ASM cells and the ECM. In addition to increased synthesis of ECM proteins, ASM cells can be involved in downregulation of matrix metalloproteinases (MMPs) and upregulation of tissue inhibitors of metalloproteinases (TIMPs), thus eventually contributing to the alteration in ECM. In turn, ECM proteins promote the survival, proliferation, cytokine synthesis, migration, and contraction of human airway smooth muscle cells. Thus, the intertwined relationship of ASM and ECM and their response to stimuli such as chronic inflammation in diseases such as asthma and COPD contribute to the remodeling seen in airways of patients with these diseases.

Authors+Show Affiliations

Parameswaran K
Firestone Institute for Respiratory Health, McMaster University and St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Willems-Widyastuti A
No affiliation info available
Alagappan VK
No affiliation info available
Radford K
No affiliation info available
Kranenburg AR
No affiliation info available
Sharma HS
No affiliation info available

MeSH

Cell MovementCell ProliferationCell SurvivalCytokinesExtracellular MatrixExtracellular Matrix ProteinsHumansModels, BiologicalMuscle RelaxationMuscle, SmoothRespiratory Physiological Phenomena

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

16456242

Citation

Parameswaran, Krishnan, et al. "Role of Extracellular Matrix and Its Regulators in Human Airway Smooth Muscle Biology." Cell Biochemistry and Biophysics, vol. 44, no. 1, 2006, pp. 139-46.
Parameswaran K, Willems-Widyastuti A, Alagappan VK, et al. Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochem Biophys. 2006;44(1):139-46.
Parameswaran, K., Willems-Widyastuti, A., Alagappan, V. K., Radford, K., Kranenburg, A. R., & Sharma, H. S. (2006). Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochemistry and Biophysics, 44(1), 139-46.
Parameswaran K, et al. Role of Extracellular Matrix and Its Regulators in Human Airway Smooth Muscle Biology. Cell Biochem Biophys. 2006;44(1):139-46. PubMed PMID: 16456242.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of extracellular matrix and its regulators in human airway smooth muscle biology. AU - Parameswaran,Krishnan, AU - Willems-Widyastuti,Anna, AU - Alagappan,Vijay K T, AU - Radford,Katherine, AU - Kranenburg,Andor R, AU - Sharma,Hari S, PY - 2006/2/4/pubmed PY - 2006/4/6/medline PY - 2006/2/4/entrez SP - 139 EP - 46 JF - Cell biochemistry and biophysics JO - Cell Biochem Biophys VL - 44 IS - 1 N2 - Altered extracellular matrix (ECM) deposition contributing to airway wall remodeling is an important feature of asthma and chronic obstructive pulmonary disease (COPD). The molecular mechanisms of this process are poorly understood. One of the key pathological features of these diseases is thickening of airway walls. This thickening is largely to the result of airway smooth muscle (ASM) cell hyperplasia and hypertrophy as well as increased deposition of ECM proteins such as collagens, elastin, laminin, and proteoglycans around the smooth muscle. Many growth factors and cytokines, including fibroblast growth factor (FGF)-1, FGF-2, and transforming growth factor (TGF)-beta1, that are released from the airway wall have the potential to contribute to airway remodeling, revealed by enhanced ASM proliferation and increased ECM protein deposition. TGF-beta1 and FGF-1 stimulate mRNA expression of collagen I and III in ASM cells, suggesting their role in the deposition of extracellular matrix proteins by ASM cells in the airways of patients with chronic lung diseases. Focus is now on the bidirectional relationship between ASM cells and the ECM. In addition to increased synthesis of ECM proteins, ASM cells can be involved in downregulation of matrix metalloproteinases (MMPs) and upregulation of tissue inhibitors of metalloproteinases (TIMPs), thus eventually contributing to the alteration in ECM. In turn, ECM proteins promote the survival, proliferation, cytokine synthesis, migration, and contraction of human airway smooth muscle cells. Thus, the intertwined relationship of ASM and ECM and their response to stimuli such as chronic inflammation in diseases such as asthma and COPD contribute to the remodeling seen in airways of patients with these diseases. SN - 1085-9195 UR - https://www.unboundmedicine.com/medline/citation/16456242/Role_of_extracellular_matrix_and_its_regulators_in_human_airway_smooth_muscle_biology_ DB - PRIME DP - Unbound Medicine ER -