Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

. 2006 Aug;35(2):252-9.
doi: 10.1165/rcmb.2006-0013OC. Epub 2006 Mar 30.

Activation of transforming growth factor-beta by the integrin alphavbeta8 delays epithelial wound closure

Claus Neurohr  1 , Stephen L Nishimura, Dean Sheppard
Affiliations

Activation of transforming growth factor-beta by the integrin alphavbeta8 delays epithelial wound closure

Claus Neurohr et al. Am J Respir Cell Mol Biol. 2006 Aug.

Abstract

Transforming growth factor (TGF)-beta family members regulate multiple aspects of wound repair through effects on cell proliferation, matrix production, and tissue inflammation, but the effects of TGF-beta on wound closure itself have been controversial. We found that blocking antibodies to TGF-beta enhanced the degree of closure of scratch wounds in primary airway epithelial monolayers, while addition of exogenous TGF-beta1 inhibited the degree of closure, suggesting that endogenous activation of TGF-beta normally serves as a brake on the degree of wound closure. Although these cells secreted large amounts of TGF-beta2 and small amounts of TGF-beta1, blockade of TGF-beta1 enhanced the degree of wound closure, whereas blockade of TGF-beta2 had no effect. TGF-beta1 (but not TGF-beta2) can be activated by two members of the integrin family, alphavbeta6 and alphavbeta8, which are both expressed on airway epithelial cells VSports手机版. Wounding induced activation of TGF-beta through effects of both integrins, but antibodies against alphavbeta8 enhanced the degree of wound closure, whereas antibodies against alphavbeta6 did not. .

PubMed Disclaimer

Figures

<b>Figure 1.</b>
Figure 1.
Effects of TGF-β1 and anti–TGF-β antibody on wound closure. (A) Phase contrast microscopy (×50 magnification) of NHBE cell monolayers on transwell culture inserts immediately after wounding (upper panels, 0 h) and after 10 h (lower panels). Incubation with either control antibody (100 μg/ml), anti-pan–TGF-β (1D11, 100 μg/ml) or TGF-β1 (10 ng/ml). Scale bar: 100 μm. (B). Degree of wound closure expressed as percent of control, 10 h after wounding. The data are shown as means ± SE. **P < 0.001 versus control.
<b>Figure 2.</b>
Figure 2.
Role of specific TGF-β iosforms in slowing epithelial wound closure. (A) Culture supernatants (apical compartment) were analyzed by ELISA for TGF-β1, TGF-β2, and TGF-β3 (logarithmic scale). TGF-β3 was not detectable (n.d.). (B) Degree of wound closure expressed as percent of control, 10 h after wounding in the absence of antibodies (control) or in the presence of blocking antibodies against all TGF-β isoforms or against TGF-β1 or -β2. **P < 0.001 versus control. (C) Unwounded NHBE (test cells) and TMLC (reporter) cells were co-cultured for 16–20 h and lysed for measurement of luciferase activity. Measurements for unwounded cells in the absence of blocking antibody were adjusted to 100%. (D) Unwounded and wounded NHBE (test cells) and TMLC (reporter) cells were co-cultured for 16–20 h in the presence or absence of blocking antibodies against all TGF-β isoforms or against TGF-β1 or -β2 and lysed for measurement of luciferase activity. Measurements for unwounded cells in the absence of blocking antibody were adjusted to 100%. The data are shown as means ± SE. *P < 0.01 versus control.
<b>Figure 3.</b>
Figure 3.
Role of specific integrins in TGF-β activation after epithelial wounding. (A) Flow cytometry of NHBE cells with and without wounding. Cells were stained with anti-αvβ5, anti-αvβ6, and anti-αvβ8 antibodies. Open peaks represent control (i.e., secondary antibody alone), shaded peaks represent NHBE cells stained with primary antibodies indicated. (B) Unwounded NHBE (test cells) and TMLC (reporter) cells were co-cultured for 16–20 h in the presence or absence of antibodies to αvβ5 (ALULA, 10 μg/ml), αvβ6 (6.3G9, 10 μg/ml), or αvβ8 (37E1, 100 μg/ml) integrins and lysed for measurement of luciferase activity. Measurements for unwounded cells in the absence of blocking antibody were adjusted to 100%. (C) Unwounded and wounded NHBE (test cells) and TMLC (reporter) cells were co-cultured for 16–20 h in the presence or absence of anti-integrin antibodies and lysed for measurement of luciferase activity. Measurements for unwounded cells in the absence of blocking antibody were adjusted to 100%. The data are shown as means ± SE. *P < 0.01 versus control.
<b>Figure 4.</b>
Figure 4.
Role of specific integrins in regulating the degree of epithelial wound closure. (A) Degree of wound closure in the presence or absence of anti-pan–TGF-β (1D11, 100 μg/ml) and antibodies to αvβ5 (ALULA, 10 μg/ml), αvβ6 (6.3G9, 10 μg/ml), or αvβ8 (37E1, 100 μg/ml) integrins, 10 h after wounding. *P < 0.01 versus control. (B) Effects of anti-αvβ6 antibody on the degree of wound closure in the presence or absence of combined treatment with antibodies against TGF-β or αvβ8, 10 h after wounding. The data are shown as means ± SE. *P < 0.01 versus treatment with either anti–TGF-β or anti-αvβ8 alone.
<b>Figure 5.</b>
Figure 5.
Effects of mitomycin C on the degree of wound closure. Degree of wound closure expressed as percent of control, 10 h after wounding and incubation with the indicated stimuli in the absence or presence of mitomycin C (MitoC, 10 μg/ml). The data are shown as means ± SE. *P < 0.01.
See this image and copyright information in PMC

References

    1. Holgate ST, Holloway J, Wilson S, Bucchieri F, Puddicombe S, Davies DE. Epithelial-mesenchymal communication in the pathogenesis of chronic asthma. Proc Am Thorac Soc 2004;1:93–98. - VSports - PubMed
    1. Selman M, King TE, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001;134:136–151. - PubMed
    1. Vilchez RA, Dauber J, Kusne S. Infectious etiology of bronchiolitis obliterans: the respiratory viruses connection—myth or reality? Am J Transplant 2003;3:245–249. - VSports手机版 - PubMed
    1. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J 2004;18:816–827. - PubMed
    1. Frank S, Madlener M, Werner S. Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing. J Biol Chem 1996;2717:10188–10193. - VSports app下载 - PubMed

VSports app下载 - Publication types

MeSH terms (VSports手机版)

"V体育官网" LinkOut - more resources