Free edges in epithelial cell sheets stimulate epidermal growth factor receptor signaling.
The ability of epithelia to migrate and cover wounds is essential to maintaining their functions as physical barriers. Wounding induces many cues that may affect the transition to motility, including the immediate mechanical perturbation, release of material from broken cells, new interactions with adjacent extracellular matrix, and breakdown of physical separation of ligands from their receptors. Depending on the exact nature of wounds, some cues may be present only transiently or insignificantly. In many epithelia, activation of the epidermal growth factor receptor (EGFR) is a central event in induction of motility, and we find that its continuous activation is required for progression of healing of wounds in sheets of corneal epithelial cells. Here, we examine the hypothesis that edges, which are universally and continuously present in wounds, are a cue. Using a novel culture model we find that their presence is sufficient to cause activation of the EGFR and increased motility of cells in the absence of other cues. Edges that are bordered by agarose do not induce activation of the EGFR, indicating that activation is not due to loss of any specific type of cell-cell interaction but rather due to loss of physical constraints.
Block
Ethan R
ER
Ophthalmology and Visual Sciences Research Center, Eye and Ear Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Tolino
Michael A
MA
Lozano
Jennifer S
JS
Lathrop
Kira L
KL
Sullenberger
Rebecca S
RS
Mazie
Abigail R
AR
Klarlund
Jes K
JK
D000255:Adenosine Triphosphate / Q000378:metabolism; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing
D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9
J Biol Chem. 1993 Feb 5;268(4):2924-31
7679104
Exp Dermatol. 2006 May;15(5):347-55
16630074
Nature. 2008 May 15;453(7193):314-21
18480812
Nat Cell Biol. 2001 May;3(5):E117-23
11331897
Biochem J. 2006 Jul 1;397(1):1-14
16761954
Invest Ophthalmol Vis Sci. 2004 Mar;45(3):813-20
14985295
Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1213-9
15284022
J Invest Dermatol. 2008 Jun;128(6):1365-74
18049451
J Cell Sci. 2007 Mar 1;120(Pt 5):815-25
17284517
Biochem Soc Trans. 2003 Dec;31(Pt 6):1203-8
14641026
Nature. 2003 Mar 20;422(6929):322-6
12646923
Biochem Biophys Res Commun. 2009 Mar 27;381(1):118-22
19232324
J Cell Sci. 2005 Jun 1;118(Pt 11):2363-70
15923649
J Cell Sci. 2003 Jun 15;116(Pt 12):2389-97
12766185
Mol Cell Biol. 2004 Jan;24(1):245-57
14673159
Methods Mol Biol. 2006;341:185-95
16799199
Curr Opin Cell Biol. 2009 Feb;21(1):47-50
19208463
Dev Biol. 1991 Oct;147(2):425-39
1655541
J Biol Chem. 2006 Oct 6;281(40):29614-24
16882662
Cornea. 2005 Nov;24(8 Suppl):S2-S11
16227819
Nat Rev Mol Cell Biol. 2009 Jan;10(1):63-73
19197333
Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):15988-93
17905871
Eur J Clin Invest. 1998 Jul;28(7):554-61
9726036
Biotechniques. 2005 Jan;38(1):73-83
15679089
Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2496-506
12766048
Prog Biophys Mol Biol. 2008 Jun-Jul;97(2-3):163-79
18406455
Development. 2005 Oct;132(19):4317-26
16141218
Curr Opin Cell Biol. 2009 Dec;21(6):864-70
19740640
Biochem Pharmacol. 2006 May 14;71(10):1422-34
16522318
Nat Rev Mol Cell Biol. 2009 Jul;10(7):445-57
19546857
Development. 2004 Jul;131(13):3021-34
15197160
Mol Med. 2007 Jan-Feb;13(1-2):30-9
17515955
Eur J Cell Biol. 2007 Dec;86(11-12):807-16
17655967
J Cell Sci. 2005 Jan 1;118(Pt 1):51-63
15585576
Annu Rev Biophys. 2009;38:217-34
19416067
Biochem Biophys Res Commun. 1997 Apr 17;233(2):389-94
9144545
J Cell Sci. 2004 May 15;117(Pt 12):2449-60
15159450
Science. 2007 Aug 3;317(5838):663-6
17673662
J Cell Sci. 2007 Mar 1;120(Pt 5):876-84
17298977
Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
19197334
Pharm Res. 2009 Nov;26(11):2369-400
19756975
Exp Eye Res. 2004 Nov;79(5):677-88
15500826
Biochem Soc Trans. 2004 Jun;32(Pt3):438-42
15157155
Invest Ophthalmol Vis Sci. 2000 May;41(6):1346-55
10798649
J Cell Sci. 2008 Oct 15;121(Pt 20):3285-92
18843115
J Cell Biol. 1999 Jul 26;146(2):517-29
10427102
Matrix Biol. 2008 Apr;27(3):220-31
18061419
Nature. 2008 Dec 18;456(7224):957-61
19078960
J Cell Sci. 2009 Apr 1;122(Pt 7):905-11
19258396
Biosystems. 2004 Aug-Oct;76(1-3):89-100
15351133
Cancer Res. 2008 Sep 15;68(18):7371-9
18794124
Curr Opin Cell Biol. 2009 Feb;21(1):38-46
19217273
Biochem J. 2009 Mar 15;418(3):491-506
19228122
J Invest Dermatol. 2004 Nov;123(5):982-9
15482488
Nat Rev Mol Cell Biol. 2004 Oct;5(10):816-26
15459662
J Cell Sci. 2004 Sep 15;117(Pt 20):4619-28
15371522
J Cell Biol. 1978 Jun;77(3):853-80
567227
Nature. 1978 Jun 1;273(5661):345-9
661946
Cell. 2006 Dec 1;127(5):1015-26
17129785
J Cell Biol. 2000 Oct 16;151(2):209-20
11038170
Exp Eye Res. 2007 Jul;85(1):130-41
17490650
Methods Cell Biol. 1998;57:251-64
9648109
Nat Cell Biol. 2008 Sep;10(9):1027-38
19160483
Kidney Int. 1995 Jul;48(1):85-92
7564096
Science. 2009 Jan 30;323(5914):638-41
19179532
Histopathology. 2002 Jan;40(1):2-11
11903593
Ann N Y Acad Sci. 2004 Dec;1030:208-18
15659800
J Biol Chem. 2002 Oct 11;277(41):38284-93
12161422
Glia. 2006 Nov 15;54(7):758-73
17006904
Mol Biol Cell. 2008 Nov;19(11):4909-17
18799627
FASEB J. 2000 Jul;14(10):1362-74
10877829
Nature. 1979 Sep 27;281(5729):259-62
551275
J Biol Chem. 2004 Jun 4;279(23):24307-12
15039441
Curr Biol. 2004 Apr 20;14(8):731-5
15084290
Biochim Biophys Acta. 2005 May 25;1755(1):37-69
15907591