HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Apparao, K. B. C. Articles by Sannes, P. L. PubMed Articles by Apparao, K. B. C. Articles by Sannes, P. L.

Sulfated Extracellular Matrix Modulates Differentiation of Human Alveolar Type II Cells In Vitro

¹ Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina

Correspondence and requests for reprints should be addressed to Philip L. Sannes, Ph.D., Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606. E-mail: philip_sannes{at}ncsu.edu

Interruption or delay in the replacement of epithelial cells in the pulmonary alveolus after injury results in faulty repair and irreversibly impaired function, often leading to fibrosis. Previous studies have shown that the key cell in this replacement, the alveolar type II cell (ATII), has an under-sulfated basal lamina, while that of the ATI cell is heavily sulfated. Since in vitro data has shown that these differences are likely to influence the ability of the ATII cell to proliferate, we hypothesized that sulfation may modulate their capacity to differentiate into ATI cells. Isolated human ATII cells were exposed to 3 µM (high concentration) heparin, a model for sulfated extracellular matrices, and RNA and protein sampled at seven time points over a 9-day period. Media/heparin was changed every 48 hours. Quantitative RT-PCR showed that heparin enhanced expression of two members of the wingless (Wnt) family of signaling proteins, Wnt7A and Wnt7B, which correlated well with Western analysis of Wnt7A and the key Wnt signaling intermediate, β-catenin. At early time points, protein expression of two members of the forkhead (Fox) family of transcription factors was elevated. FoxA1 was increased specifically by heparin through 96 hours, while FoxA2 was elevated from 24 hours through 7 days of culture. FoxP2 appeared at 72 hours and steadily increased through Day 9 of culture. FoxA2 and FoxP2 were only partially reduced by heparin. Wnt7A, Wnt7B, FoxA1, FoxA2, and FoxP2 have all been shown to play important roles in alveolar morphogenesis during early lung development. These collective data suggest they may also play roles in adult alveolar epithelial cell differentiation as well, and could be useful targets for gene manipulation for the purpose of altering fibrogenic outcomes.

FOOTNOTES

Supported by PHS grant HL44497 (P.L.S.) and the State of North Carolina.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form August 29, 2007; accepted in final form October 16, 2007)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Apparao, K. B. C. Articles by Sannes, P. L. PubMed Articles by Apparao, K. B. C. Articles by Sannes, P. L.