HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text Free Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Evans, S. E. Articles by Limper, A. H. Search for Related Content PubMed PubMed Citation Articles by Evans, S. E. Articles by Limper, A. H.

Transforming Growth Factor-ß₁ and Extracellular Matrix-Associated Fibronectin Expression in Pulmonary Lymphangioleiomyomatosis^*

^* From the Thoracic Diseases Research Unit (Drs. Evans, Ryu, and Limper), Division of Pulmonary & Critical Care, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN; and the Department of Laboratory Medicine and Pathology (Dr. Colby), Mayo Clinic, Scottsdale, AZ.

Correspondence to: Andrew H. Limper, MD, FCCP, 8-24 Stabile Building, Mayo Clinic, Rochester, MN, 55905; e-mail limper.andrew@mayo.edu

Study objectives: Lymphangioleiomyomatosis (LAM) is a rare disorder of unknown etiology, affecting almost exclusively women of childbearing age, that is associated with the proliferation of spindle cells and cystic changes in the affected lung. The underlying processes that contribute to this disease are poorly understood. Transforming growth factor (TGF)-ß₁ is a potent cytokine that promotes mesenchymal cell proliferation and regulates the synthesis of extracellular matrix (ECM) components, particularly fibronectins. Herein, we evaluate the expression of TGFß₁ and matrix-associated fibronectin in lung specimens demonstrating LAM.

Design: Lung biopsy specimens that were confirmed to contain pathologic LAM cells were obtained from 13 patients. The specimens were submitted to immunohistochemical evaluation for TGFß₁ and fibronectin, as well as the typical markers of LAM cells. Healthy lung parenchyma surrounding resected neoplasms was studied in a parallel fashion as control tissues.

Measurements and results: In all 13 LAM cases and in healthy lung parenchyma, we demonstrated that TGFß₁ localized consistently to airway epithelial cells. However, in LAM tissues, matrix-associated TGFß₁ was also consistently found in regions containing pathologic LAM cells. Notably, more abundant TGFß₁ was observed in highly cellular areas compared to the walls of chronic cystic regions in LAM tissues. Fibronectin, a matrix component that is strongly expressed in response to active TGFß₁ was found to consistently colocalize with this protein in these highly cellular regions, supporting TGFß₁ activity in these regions. The markers of proliferating LAM cells, including proliferating cell nuclear antigen, were also markedly present in these highly cellular LAM regions.

Conclusion: These studies suggest that the proliferation of aberrant LAM cells may be associated with altered regional expression of TGFß₁ and related ECM proteins.

Key Words: fibronectins • lymphangioleiomyomatosis • transforming growth factor-ß

This article has been cited by other articles:

				B. Camoretti-Mercado, D. J. Fernandes, S. Dewundara, J. Churchill, L. Ma, P. C. Kogut, J. F. McConville, M. S. Parmacek, and J. Solway Inhibition of Transforming Growth Factor beta-enhanced Serum Response Factor-dependent Transcription by SMAD7 J. Biol. Chem., July 21, 2006; 281(29): 20383 - 20392. [Abstract] [Full Text] [PDF]

				J. L. Black, Q. Ge, S. Boustany, P. R. A. Johnson, M. H. Poniris, A. R. Glanville, B. G. G. Oliver, L. M. Moir, and J. K. Burgess In vitro studies of lymphangioleiomyomatosis Eur. Respir. J., October 1, 2005; 26(4): 569 - 576. [Abstract] [Full Text] [PDF]