title: Inhibitor of differentiation 1 promotes endothelial survival in a bleomycin model of lung injury in mice.
abstract: The Id family of genes encodes negative regulators of basic helix-loop-helix transcription factors and has been implicated in diverse cellular processes such as proliferation, apoptosis, differentiation, and migration. However, the specific role of Id1 in lung injury has not been investigated. Bleomycin has been widely used to generate animal models of acute lung injury and fibrogenesis. In this study we found that, on bleomycin challenge, Id1 expression was significantly up-regulated in the lungs, predominantly in endothelial cells, as revealed by double immunolabeling and quantitative flow cytometric analysis. Mice with Id1 loss-of-function (Id1(-/-)) displayed increased vascular permeability and endothelial apoptosis in the lungs after bleomycin-induced injury. Cultured Id1(-/-) lung microvascular endothelial cells also showed decreased survival when exposed to bleomycin. We detected a decrease in the level of Bcl-2, a primary anti-apoptotic protein, in Id1(-/-) endothelial cells, suggesting that down-regulated Bcl-2 may promote endothelial apoptosis in the lung. Therefore, we propose that Id1 plays a crucial role in promoting endothelial survival in the adult lung on injury. In addition, bleomycin-exposed Id1(-/-) mice showed increased lung collagen accumulation and fibrogenesis, suggesting that Id1 up-regulation in the lung may play a critical role in lung homeostasis.
authors: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 4114 MRB III, Nashville, TN 37232, USA.
authors: Huimin
authors: H
authors: Zhang
authors: William E
authors: WE
authors: Lawson
authors: Vasiliy V
authors: VV
authors: Polosukhin
authors: Ambra
authors: A
authors: Pozzi
authors: Timothy S
authors: TS
authors: Blackwell
authors: Ying
authors: Y
authors: Litingtung
authors: Chin
authors: C
authors: Chiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001761:Bleomycin / Q000633:toxicity; D002470:Cell Survival; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*
chemical_list: C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D019253:Proto-Oncogene Proteins c-bcl-2; D001761:Bleomycin; D003094:Collagen; D020930:MAP Kinase Kinase Kinases
references: Nat Rev Mol Cell Biol. 2002 May;3(5):349-63
references: 11988769
references: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Suppl):S87-92
references: 14503563
references: Shock. 2007 Mar;27(3):266-73
references: 17304107
references: Carcinogenesis. 2004 Jun;25(6):881-7
references: 14742319
references: Am Rev Respir Dis. 1992 Jun;145(6):1495-8
references: 1596025
references: Genesis. 2000 Nov-Dec;28(3-4):147-55
references: 11105057
references: Am J Pathol. 1994 Jul;145(1):114-25
references: 7518191
references: Nature. 1999 Oct 14;401(6754):670-7
references: 10537105
references: Chest. 2002 Dec;122(6 Suppl):286S-289S
references: 12475801
references: Mod Pathol. 2002 Oct;15(10):1058-67
references: 12379752
references: Oncogene. 2003 Jul 17;22(29):4498-508
references: 12881706
references: Hum Immunol. 2006 Apr-May;67(4-5):284-97
references: 16720208
references: Eur J Nucl Med Mol Imaging. 2005 Feb;32(2):221-8
references: 15449048
references: J Biol Chem. 1999 Jul 9;274(28):19838-45
references: 10391928
references: Am J Clin Pathol. 2003 Apr;119(4):556-67
references: 12710128
references: Radiat Res. 1989 Oct;120(1):113-20
references: 2552496
references: Radiat Res. 1992 Feb;129(2):139-48
references: 1734443
references: Exp Toxicol Pathol. 1996 Jun;48(4):283-8
references: 8811296
references: Nat Med. 2001 Nov;7(11):1194-201
references: 11689883
references: Mol Cell Biol. 1991 Nov;11(11):5603-11
references: 1922066
references: Ann Intern Med. 2001 Jan 16;134(2):136-51
references: 11177318
references: Am Rev Respir Dis. 1989 Dec;140(6):1693-703
references: 2604297
references: Am J Respir Crit Care Med. 2005 Apr 15;171(8):899-907
references: 15618458
references: Int J Oncol. 2003 Mar;22(3):469-80
references: 12579299
references: Circ Res. 2005 Sep 2;97(5):496-504
references: 16100039
references: Am J Respir Crit Care Med. 2005 Feb 1;171(3):261-8
references: 15502109
references: J Clin Invest. 2001 Jun;107(12):1537-44
references: 11413161
references: Thorax. 2000 Feb;55(2):147-52
references: 10639534
references: EMBO J. 2004 Feb 11;23(3):541-51
references: 14739937
references: Circ Res. 2000 Mar 31;86(6):692-9
references: 10747006
references: Lab Invest. 1992 Aug;67(2):234-42
references: 1380105
references: Cancer Lett. 2004 Feb 20;204(2):189-96
references: 15013218
references: Nat Rev Cancer. 2005 Feb;5(2):102-12
references: 15685195
references: Oncogene. 2001 Oct 25;20(48):7085-95
references: 11704832
references: Exp Toxicol Pathol. 2004 Jul;55(6):497-503
references: 15384255
references: Oncogene. 2001 Dec 20;20(58):8317-25
references: 11840324
references: Am J Pathol. 1996 Feb;148(2):527-37
references: 8579115
references: Mol Cell. 2003 Apr;11(4):915-26
references: 12718878
references: Nat Genet. 1998 Sep;20(1):58-61
references: 9731532
references: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7812-6
references: 11427735
references: Dev Biol. 1995 Nov;172(1):126-38
references: 7589793
references: Circulation. 2005 Nov 1;112(18):2840-50
references: 16267257
references: Dev Dyn. 1996 Nov;207(3):235-52
references: 8922523
references: Am J Respir Cell Mol Biol. 2005 Jul;33(1):9-13
references: 15964990
references: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6548-53
references: 16611729
references: Mol Cell Biol. 2004 May;24(10):4241-54
references: 15121845
references: Int J Exp Pathol. 1994 Oct;75(5):321-8
references: 7528044
references: Am J Respir Cell Mol Biol. 1995 Jul;13(1):34-44
references: 7541221
references: J Cell Biochem. 2003 Jun 1;89(3):474-83
references: 12761881
references: Cancer Res. 2006 Nov 15;66(22):10870-7
references: 17108123
references: Apoptosis. 2004 May;9(3):279-89
references: 15258459
references: Glia. 1999 Apr;26(2):139-52
references: 10384879
references: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1260-5
references: 17227850
references: Chest. 2004 Feb;125(2):754-65
references: 14769761
references: J Inflamm (Lond). 2005 May 28;2(1):4
references: 15921526
references: Am J Respir Crit Care Med. 1995 Jun;151(6):1946-55
references: 7767544
references: J Cell Biol. 1993 Jul;122(1):103-11
references: 8314838
references: Annu Rev Med. 2007;58:285-98
references: 16886904
references: J Pathol. 2002 Nov;198(3):388-96
references: 12375272
references: Am J Respir Crit Care Med. 2005 Apr 15;171(8):889-98
references: 15563636
references: Science. 2001 Sep 28;293(5539):2449-52
references: 11498544
references: Nat Rev Immunol. 2001 Dec;1(3):193-9
references: 11905828
references: Circulation. 2003 Sep 9;108 Suppl 1:II348-53
references: 12970258
references: Adv Cancer Res. 2004;92:81-94
references: 15530557
references: Clin Biochem. 1996 Jun;29(3):225-9
references: 8740508
references: Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L585-93
references: 11839555
references: J Cell Sci. 2001 Feb;114(Pt 4):671-6
references: 11171372
references: Sarcoidosis Vasc Diffuse Lung Dis. 2005 Dec;22 Suppl 1:S15-23
references: 16457013
references: Exp Lung Res. 2002 Sep;28(6):405-17
references: 12217209
references: Circulation. 2002 Oct 22;106(17):2263-70
references: 12390958
references: Front Biosci. 2007;12:3117-24
references: 17485286
references: Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2202-7
references: 10681423
references: Trends Cell Biol. 2003 Aug;13(8):410-8
references: 12888293
references: Am Rev Respir Dis. 1989 Oct;140(4):1104-7
references: 2478057
references: Development. 1997 Jan;124(1):53-63
references: 9006067
references: Am J Pathol. 2003 Feb;162(2):533-46
references: 12547711
references: Biochem Biophys Res Commun. 1996 Aug 5;225(1):161-6
references: 8769111
references: Lab Invest. 2002 Aug;82(8):1073-9
references: 12177246
references: Eur J Nucl Med. 1989;15(4):207-10
references: 2753053
references: Am J Respir Crit Care Med. 2003 Feb 1;167(3):438-43
references: 12406847
references: Cancer Res. 2004 Sep 1;64(17):6137-43
references: 15342397
references: Carcinogenesis. 2005 Oct;26(10):1668-76
references: 15905202
references: J Clin Invest. 1999 Jul;104(1):5-11
references: 10393693
references: Am J Pathol. 2005 Nov;167(5):1267-77
references: 16251411
references: J Immunol. 2005 Jun 1;174(11):7014-21
references: 15905544
references: Anesth Analg. 2005 Apr;100(4):929-36
references: 15781500
references: Int J Cancer. 2006 Aug 1;119(3):508-14
references: 16506209
references: EMBO J. 2002 Apr 2;21(7):1743-53
references: 11927558
references: Nature. 2001 Sep 6;413(6851):86-91
references: 11544531
references: Oncogene. 2001 Dec 20;20(58):8334-41
references: 11840326