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

J. Biol. Chem., Vol. 282, Issue 6, 3968-3976, February 9, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/6/3968    most recent M609060200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bhaskaran, M. Articles by Liu, L. Search for Related Content PubMed PubMed Citation Articles by Bhaskaran, M. Articles by Liu, L. Social Bookmarking                      What's this?

Trans-differentiation of Alveolar Epithelial Type II Cells to Type I Cells Involves Autocrine Signaling by Transforming Growth Factor 1 through the Smad Pathway^*

From the Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078

Type II alveolar epithelial cells (AEC II) proliferate and transdifferentiate into type I alveolar epithelial cells (AEC I) when the normal AEC I population is damaged in the lung alveoli. We hypothesized that signaling by transforming growth factor 1 (TGF 1), through its downstream Smad proteins, is involved in keeping AEC II quiescent in normal cells and its altered signaling may be involved in the trans-differentiation of AEC II to AEC I. In the normal lung, TGF 1 and Smad4 were highly expressed in AEC II. Using an in vitro cell culture model, we demonstrated that the trans-differentiation of AEC II into AEC I-like cells began with a proliferative phase, followed by a differentiation phase. The expression of TGF 1, Smad2, and Samd3 and their phosphorylated protein forms, and cell cycle inhibitors, p15^Ink4b and p21^Cip1, was lower during the proliferative phase but higher during the differentiation phase. Furthermore, cyclin-dependent kinases 2, 4, and 6 showed an opposite trend of expression. TGF 1 secretion into the media increased during the differentiation phase, indicating an autocrine regulation. The addition of TGF 1 neutralizing antibody after the proliferative phase and silencing of Smad4 by RNA interference inhibited the trans-differentiation process. In summary, our results suggest that the trans-differentiation of AEC II to AEC I is modulated by signaling through the Smad-dependent TGF 1 pathway by altering the expression of proteins that control the G₁ to S phase entry in the cell cycle.

Received for publication, September 25, 2006 , and in revised form, December 6, 2006.

^* This work was supported by National Institutes of Health Grants R01 HL-052146, R01 HL-083188, and R01 HL-071628 (to L. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: 264 McElroy Hall, Stillwater, OK 74078. Tel.: 405-744-4526; Fax: 405-744-8263; E-mail: lin.liu{at}okstate.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Yamazaki, S. Komazaki, H. Nakanishi, A. Mishima, M. Nishi, M. Yazawa, T. Yamazaki, R. Taguchi, and H. Takeshima Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation Development, July 15, 2009; 136(14): 2355 - 2361. [Abstract] [Full Text] [PDF]

				L. M. Marsh, L. Cakarova, G. Kwapiszewska, W. von Wulffen, S. Herold, W. Seeger, and J. Lohmeyer Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L442 - L452. [Abstract] [Full Text] [PDF]

				D.M. Raiser, S.J. Zacharek, R.R. Roach, S.J. Curtis, K.W. Sinkevicius, D.W. Gludish, and C.F. Kim Stem Cell Biology in the Lung and Lung Cancers: Employing Pulmonary Context and Classic Approaches Cold Spring Harb Symp Quant Biol, November 26, 2008; (2008) sqb.2008.73.036v2. [Abstract] [PDF]

				M. N. Helms, L. Jain, J. L. Self, and D. C. Eaton Redox Regulation of Epithelial Sodium Channels Examined in Alveolar Type 1 and 2 Cells Patch-clamped in Lung Slice Tissue J. Biol. Chem., August 15, 2008; 283(33): 22875 - 22883. [Abstract] [Full Text] [PDF]

				H. Chen, F. Zhuang, Y-H. Liu, B. Xu, P. del Moral, W. Deng, Y. Chai, M. Kolb, J. Gauldie, D. Warburton, et al. TGF-{beta} receptor II in epithelia versus mesenchyme plays distinct roles in the developing lung Eur. Respir. J., August 1, 2008; 32(2): 285 - 295. [Abstract] [Full Text] [PDF]

				S. Buckley, W. Shi, L. Barsky, and D. Warburton TGF-{beta} signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L739 - L748. [Abstract] [Full Text] [PDF]

				S. R. Bates, J.-Q. Tao, K. J. Yu, Z. Borok, E. D. Crandall, H. L. Collins, and G. H. Rothblat Expression and Biological Activity of ABCA1 in Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 283 - 292. [Abstract] [Full Text] [PDF]