Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Autoimmunity/*physiology ; Epithelial-Mesenchymal Transition/*physiology ; Fibrosis/*metabolism ; Inflammation/*metabolism ; Transforming Growth Factor beta/*metabolism; Animals ; Autoimmunity/genetics ; Epithelial-Mesenchymal Transition/genetics ; Fibrosis/genetics ; Humans ; Inflammation/genetics

Recent advances in our understanding of the molecular pathways that control the link of inflammation with organ fibrosis and autoimmune diseases point to the epithelial to mesenchymal transition (EMT) as the common association in the progression of these diseases characterized by an intense inflammatory response. EMT, a process in which epithelial cells are gradually transformed to mesenchymal cells, is a major contributor to the pathogenesis of fibrosis. Importantly, the chronic inflammatory microenvironment has emerged as a decisive factor in the induction of pathological EMT. Transforming growth factor-β (TGF-β), a multifunctional cytokine, plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases, contributing to marked fibrotic changes that severely impair normal tissue architecture and function. The understanding of molecular mechanisms underlying EMT-dependent fibrosis has both a basic and a translational relevance, since it may be useful to design therapies aimed at counteracting organ deterioration and failure. To this end, we reviewed the recent literature to better elucidate the molecular response to inflammatory/fibrogenic signals in autoimmune diseases in order to further the specific regulation of EMT-dependent fibrosis in more targeted therapies.

Crit Rev Clin Lab Sci. 2004;41(3):233-64. (PMID: 15307633)
J Clin Invest. 2014 Apr;124(4):1622-35. (PMID: 24590289)
Histochem Cell Biol. 2018 Aug;150(2):133-147. (PMID: 29789993)
Am J Pathol. 2014 May;184(5):1369-83. (PMID: 24631025)
Diabetes. 2006 Sep;55(9):2611-9. (PMID: 16936211)
Cytokine Growth Factor Rev. 2011 Jun;22(3):131-9. (PMID: 21757394)
Mol Immunol. 2018 Jul;99:134-144. (PMID: 29783158)
J Immunol. 2002 Jul 1;169(1):587-94. (PMID: 12077292)
Cell. 1997 Jun 27;89(7):1165-73. (PMID: 9215638)
EMBO J. 2001 Aug 1;20(15):4132-42. (PMID: 11483516)
Exp Cell Res. 2001 Mar 10;264(1):169-84. (PMID: 11237532)
Annu Rev Cell Dev Biol. 2005;21:659-93. (PMID: 16212511)
Am J Physiol Renal Physiol. 2010 May;298(5):F1263-75. (PMID: 20015942)
FASEB J. 2004 Jan;18(1):176-8. (PMID: 12709399)
Nat Med. 2010 Dec;16(12):1400-6. (PMID: 21102460)
J Am Soc Nephrol. 2002 Oct;13(10):2600-10. (PMID: 12239251)
Am J Pathol. 2016 Feb;186(2):359-74. (PMID: 26704941)
J Am Soc Nephrol. 2008 Dec;19(12):2282-7. (PMID: 18987304)
J Clin Invest. 2009 Jun;119(6):1438-49. (PMID: 19487820)
Metabolism. 2000 Mar;49(3):353-9. (PMID: 10726914)
Pathol Oncol Res. 2009 Jun;15(2):251-6. (PMID: 19020994)
Cancer Res. 2006 Feb 15;66(4):2202-9. (PMID: 16489022)
Clin Transl Med. 2014 Jul 15;3:23. (PMID: 25097726)
Reumatol Clin. 2014 May-Jun;10(3):174-9. (PMID: 24685296)
Circ Res. 2016 Mar 18;118(6):1021-40. (PMID: 26987915)
Int J Inflam. 2011;2011:724080. (PMID: 22187661)
Nature. 2021 Jan;589(7841):281-286. (PMID: 33176333)
J Biochem. 2007 Mar;141(3):345-51. (PMID: 17301079)
Nephrol Dial Transplant. 2002 Dec;17(12):2145-52. (PMID: 12454225)
Cell Physiol Biochem. 2014;34(2):356-67. (PMID: 25060912)
Future Oncol. 2009 Oct;5(8):1145-68. (PMID: 19852727)
Front Immunol. 2019 Jun 19;10:1395. (PMID: 31275325)
Nat Rev Nephrol. 2016 Jun;12(6):325-38. (PMID: 27108839)
Mol Cell Biol. 2011 Jun;31(12):2392-403. (PMID: 21482667)
Mol Cell Biol. 2006 Jan;26(2):654-67. (PMID: 16382155)
Nature. 1997 Oct 9;389(6651):631-5. (PMID: 9335507)
Am J Physiol. 1999 Apr;276(4):G1059-68. (PMID: 10198351)
Osteoarthritis Cartilage. 2004 Apr;12(4):296-305. (PMID: 15023381)
J Clin Invest. 2009 Jun;119(6):1420-8. (PMID: 19487818)
Mult Scler. 2003 Dec;9(6):540-9. (PMID: 14664465)
J Cell Biol. 2015 May 25;209(4):493-506. (PMID: 26008742)
Diabetes Care. 2010 Jan;33(1):55-60. (PMID: 19808918)
Kidney Int. 1996 Feb;49(2):461-9. (PMID: 8821830)
Front Immunol. 2018 Nov 02;9:2537. (PMID: 30450102)
Curr Neuropharmacol. 2008 Sep;6(3):179-92. (PMID: 19506719)
Int J Mol Med. 2018 Aug;42(2):851-860. (PMID: 29750298)
Cell Res. 2009 Jan;19(1):8-20. (PMID: 19114991)
J Biol Chem. 2003 Jun 6;278(23):21113-23. (PMID: 12665527)
J Cell Biochem. 2007 Jul 1;101(4):830-9. (PMID: 17211838)
Ann Rheum Dis. 2013 May;72(5):782-3. (PMID: 23264342)
J Biol Chem. 2010 Jun 25;285(26):20202-12. (PMID: 20363741)
Cold Spring Harb Perspect Biol. 2016 Oct 3;8(10):. (PMID: 27449814)
Diabetes. 1997 May;46(5):854-9. (PMID: 9133555)
J Exp Med. 1990 Jan 1;171(1):231-47. (PMID: 2295877)
Hepatology. 2007 Oct;46(4):1257-70. (PMID: 17657819)
Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L525-34. (PMID: 17631612)
Cancer Sci. 2007 Oct;98(10):1512-20. (PMID: 17645776)
Kidney Int Suppl. 2003 Nov;(87):S99-104. (PMID: 14531781)
Exp Biol Med (Maywood). 2016 Jan;241(1):1-13. (PMID: 26361988)
J Biol Chem. 2013 May 24;288(21):14824-38. (PMID: 23589287)
PLoS One. 2016 Apr 28;11(4):e0154419. (PMID: 27123854)
FEBS J. 2016 Jun;283(12):2219-32. (PMID: 26807763)
N Engl J Med. 2001 Sep 20;345(12):851-60. (PMID: 11565517)
Am J Kidney Dis. 2015 Nov;66(5):e37-8. (PMID: 26498421)
Gastroenterology. 2006 Dec;131(6):1786-98. (PMID: 17087939)
Nat Cell Biol. 1999 Sep;1(5):260-6. (PMID: 10559937)
Immunol Rev. 2012 Jul;248(1):87-103. (PMID: 22725956)
J Am Soc Nephrol. 2002 Nov;13(11):2657-66. (PMID: 12397035)
Rev Diabet Stud. 2012 Spring;9(1):23-35. (PMID: 22972442)
N Engl J Med. 1994 Nov 10;331(19):1286-92. (PMID: 7935686)
J Biochem. 2010 Jun;147(6):781-92. (PMID: 20410014)
Gastroenterology. 2008 Aug;135(2):642-59. (PMID: 18602923)
J Pathol. 2008 Jan;214(2):199-210. (PMID: 18161745)
Curr Opin Neurol. 2005 Jun;18(3):225-30. (PMID: 15891404)
Int J Exp Pathol. 2011 Jun;92(3):143-50. (PMID: 21554437)
Clin Exp Immunol. 1999 Jan;115(1):176-82. (PMID: 9933439)
Am J Kidney Dis. 2001 Oct;38(4):761-9. (PMID: 11576879)
J Med. 1996;27(3-4):103-13. (PMID: 8982960)
Mol Pathol. 2003 Feb;56(1):52-9. (PMID: 12560464)
Nat Rev Immunol. 2007 Jun;7(6):443-53. (PMID: 17525753)
J Clin Invest. 2003 Nov;112(10):1486-94. (PMID: 14617750)
J Cell Biol. 1962 Aug;14:207-20. (PMID: 13865038)
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2918-21. (PMID: 2011600)
Am Fam Physician. 2004 Nov 15;70(10):1935-44. (PMID: 15571060)
Cell Death Dis. 2019 Jan 18;10(2):45. (PMID: 30718504)
J Hepatol. 1998 May;28(5):803-11. (PMID: 9625315)
Nat Immunol. 2007 Dec;8(12):1390-7. (PMID: 17994024)
Diabetes Metab Res Rev. 2011 May;27(4):311-7. (PMID: 21309056)
Nature. 2005 Jul 7;436(7047):123-7. (PMID: 16001073)
Kidney Int. 2009 Mar;75(5):475-81. (PMID: 18716603)
Mol Cell Biochem. 2019 Sep;459(1-2):141-150. (PMID: 31297660)
J Clin Invest. 2011 Feb;121(2):468-74. (PMID: 21370523)
Nat Commun. 2017 Feb 09;8:14361. (PMID: 28181491)
J Biol Chem. 2004 Aug 27;279(35):37004-12. (PMID: 15213232)
Acta Neuropathol. 2011 Nov;122(5):601-14. (PMID: 21983942)
J Cell Biol. 1994 Dec;127(6 Pt 2):2021-36. (PMID: 7806579)
J Pathol. 2003 Oct;201(2):319-27. (PMID: 14517850)
Acta Odontol Latinoam. 2016 Sep;29(2):138-143. (PMID: 27731483)
Am J Physiol Renal Physiol. 2012 Sep;303(5):F733-45. (PMID: 22759394)
Arthritis Res Ther. 2016 Dec 1;18(1):279. (PMID: 27906049)
J Immunol. 1998 Mar 1;160(5):2539-45. (PMID: 9498800)
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8015-20. (PMID: 10859350)
Annu Rev Cell Dev Biol. 2011;27:347-76. (PMID: 21740232)
J Histochem Cytochem. 2016 Mar;64(3):157-67. (PMID: 26747705)
Respir Res. 2007 Jan 07;8:1. (PMID: 17207287)
J Biol Chem. 1994 Oct 28;269(43):26775-82. (PMID: 7929413)
Front Physiol. 2012 Mar 19;3:53. (PMID: 22457652)
J Pathol. 2003 Nov;201(3):343-54. (PMID: 14595745)
Cold Spring Harb Perspect Biol. 2016 Aug 01;8(8):. (PMID: 27481709)
Arch Immunol Ther Exp (Warsz). 2020 Sep 10;68(5):27. (PMID: 32914376)
J Clin Invest. 1991 Mar;87(3):1108-13. (PMID: 1999490)
J Biol Chem. 2007 Aug 10;282(32):23337-47. (PMID: 17562716)
Genes Dev. 2000 Jan 15;14(2):163-76. (PMID: 10652271)
Biochem Biophys Res Commun. 2003 Jun 13;305(4):1002-7. (PMID: 12767930)
J Am Soc Nephrol. 2010 Feb;21(2):212-22. (PMID: 20019167)
J Clin Invest. 2009 Jun;119(6):1429-37. (PMID: 19487819)
Lupus. 1995 Aug;4(4):286-92. (PMID: 8528225)
J Biol Chem. 2007 Jul 27;282(30):22089-101. (PMID: 17513865)
Am J Physiol Renal Physiol. 2010 Sep;299(3):F545-58. (PMID: 20576680)
Biol Chem. 2004 Jul;385(7):649-53. (PMID: 15318814)
Biochim Biophys Acta. 2016 Mar;1862(3):452-60. (PMID: 26493443)
Dev Cell. 2008 Jun;14(6):818-29. (PMID: 18539112)
Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3):. (PMID: 27920040)
Trends Immunol. 2005 Nov;26(11):572-9. (PMID: 16153890)
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96. (PMID: 24556840)
Lupus. 1999;8(2):90-4. (PMID: 10192501)
Clin Exp Rheumatol. 2001 Mar-Apr;19(2):131-7. (PMID: 11326474)
J Clin Invest. 2008 Aug;118(8):2722-32. (PMID: 18618014)
Hepatology. 2014 Feb;59(2):630-42. (PMID: 23959575)
Eur Respir J. 2017 Feb 23;49(2):. (PMID: 28182573)
J Clin Invest. 2005 Feb;115(2):209-18. (PMID: 15690074)
Arthritis Res Ther. 2006;8(6):R165. (PMID: 17076892)
Lupus. 2012 Mar;21(3):310-8. (PMID: 22072025)
Immunol Invest. 2012;41(1):15-27. (PMID: 21563925)
Diabetes. 2010 Oct;59(10):2612-24. (PMID: 20682692)
Respir Res. 2020 Feb 18;21(1):56. (PMID: 32070329)
J Neuropathol Exp Neurol. 1999 Feb;58(2):174-87. (PMID: 10029100)
Eur J Rheumatol. 2014 Jun;1(2):86-87. (PMID: 27708883)
PLoS One. 2015 May 08;10(5):e0123641. (PMID: 25955532)
Nat Cell Biol. 2017 Oct;19(10):1133-1141. (PMID: 28945230)
J Rheumatol. 2010 Oct;37(10):2039-45. (PMID: 20682675)
Lab Invest. 2007 Nov;87(11):1077-91. (PMID: 17724448)
Mol Cell Endocrinol. 2005 Nov 24;243(1-2):19-26. (PMID: 16219413)
Lancet. 2011 Dec 3;378(9807):1949-61. (PMID: 21719092)
Lab Invest. 2020 Jun;100(6):824-836. (PMID: 31925325)
Am J Pathol. 2009 Oct;175(4):1380-8. (PMID: 19729486)
Am J Pathol. 2003 May;162(5):1495-502. (PMID: 12707032)
Eur J Immunol. 1999 Mar;29(3):1004-13. (PMID: 10092105)
Therap Adv Gastroenterol. 2016 Jul;9(4):527-32. (PMID: 27366221)
Nat Rev Cancer. 2002 Jun;2(6):442-54. (PMID: 12189386)
Int J Biochem Cell Biol. 2005 Jan;37(1):38-41. (PMID: 15381147)
Arthritis Res Ther. 2003;5(3):R132-9. (PMID: 12723985)
Mucosal Immunol. 2018 Mar;11(2):294-303. (PMID: 29346350)
Front Oncol. 2018 Sep 10;8:357. (PMID: 30250825)
PLoS One. 2013;8(1):e54001. (PMID: 23342059)
Mediators Inflamm. 2018 Nov 26;2018:1965935. (PMID: 30598637)
J Clin Invest. 1997 Aug 15;100(4):768-76. (PMID: 9259574)
Front Cell Dev Biol. 2020 Mar 24;8:187. (PMID: 32266267)
Cell. 1999 Feb 5;96(3):319-28. (PMID: 10025398)
Toxicol Appl Pharmacol. 2015 Mar 1;283(2):75-82. (PMID: 25595642)
Front Pharmacol. 2019 Apr 18;10:388. (PMID: 31057405)
Epilepsia. 2012 Nov;53 Suppl 6:45-52. (PMID: 23134495)
Vasc Health Risk Manag. 2008;4(3):575-96. (PMID: 18827908)
Lab Invest. 1993 Feb;68(2):154-63. (PMID: 8441250)
Cell. 2009 Nov 25;139(5):871-90. (PMID: 19945376)
Arch Neurol. 2002 Mar;59(3):391-7. (PMID: 11890842)
Nat Med. 2003 Jul;9(7):964-8. (PMID: 12808448)
J Clin Invest. 1993 Aug;92(2):632-7. (PMID: 7688761)
Diabetes. 1996 Apr;45(4):522-30. (PMID: 8603776)
J Biol Chem. 2013 Oct 18;288(42):30708-30719. (PMID: 24005672)
Curr Eye Res. 1994 Dec;13(12):885-90. (PMID: 7720396)
Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. (PMID: 21471066)
Cell Res. 2009 Jan;19(1):128-39. (PMID: 19114990)
Br J Cancer. 2008 Nov 4;99(9):1375-9. (PMID: 18797460)
J Clin Invest. 2003 Dec;112(12):1776-84. (PMID: 14679171)
J Immunol. 1990 Jun 1;144(11):4189-94. (PMID: 2187926)
Mol Biol Cell. 2005 Apr;16(4):1987-2002. (PMID: 15689496)
Respir Res. 2013 Nov 01;14:118. (PMID: 24283210)
Genes Dev. 2006 Nov 15;20(22):3130-46. (PMID: 17114584)
N Engl J Med. 2018 Mar 08;378(10):931-939. (PMID: 29514034)
Trends Immunol. 2010 Mar;31(3):110-9. (PMID: 20106721)
Immunology. 2006 May;118(1):10-24. (PMID: 16630019)
Sci Rep. 2018 Aug 9;8(1):11920. (PMID: 30093732)
Semin Cell Dev Biol. 2008 Jun;19(3):294-308. (PMID: 18343170)
Kidney Int. 1994 Mar;45(3):916-27. (PMID: 8196298)
Immunol Rev. 2006 Aug;212:185-202. (PMID: 16903915)
J Clin Invest. 2011 Jan;121(1):277-87. (PMID: 21135509)
ScientificWorldJournal. 2014 Jan 21;2014:521754. (PMID: 24578639)
Arthritis Res Ther. 2006;8(3):210. (PMID: 16689999)
Am J Pathol. 2013 Jan;182(1):118-31. (PMID: 23142380)
Cell Tissue Res. 2012 Jan;347(1):103-16. (PMID: 21845400)
J Clin Invest. 2002 Aug;110(3):341-50. (PMID: 12163453)
Cold Spring Harb Perspect Biol. 2017 Feb 1;9(2):. (PMID: 27864313)
J Exp Clin Cancer Res. 2014 Aug 02;33:62. (PMID: 25084828)
J Exp Med. 1993 Jan 1;177(1):225-30. (PMID: 8418203)
J Am Soc Nephrol. 2015 Apr;26(4):817-29. (PMID: 25535303)
Growth Factors. 2011 Oct;29(5):196-202. (PMID: 21740331)
Am J Physiol Gastrointest Liver Physiol. 2013 Dec;305(12):G881-90. (PMID: 24157970)
Clin Exp Metastasis. 2004;21(3):235-42. (PMID: 15387373)
J Am Soc Nephrol. 1998 Dec;9(12):2253-61. (PMID: 9848779)
J Cell Sci. 2010 Dec 15;123(Pt 24):4231-9. (PMID: 21081648)
Front Biosci. 2008 May 01;13:6991-8. (PMID: 18508710)
Bone Res. 2018 Apr 27;6:15. (PMID: 29736302)
J Nephrol. 2006 Jul-Aug;19(4):407-12. (PMID: 17048197)
Am J Respir Crit Care Med. 2009 Oct 1;180(7):657-65. (PMID: 19556518)
PLoS One. 2008 Sep 16;3(9):e3220. (PMID: 18795102)
Clin Exp Rheumatol. 1998 Jan-Feb;16(1):63-5. (PMID: 9543564)
Nat Med. 2013 Dec;19(12):1584-96. (PMID: 24309662)
J Cell Sci. 1999 Dec;112 ( Pt 24):4557-68. (PMID: 10574705)
Clin Exp Immunol. 2019 Nov;198(2):261-272. (PMID: 31165469)
J Clin Invest. 2015 Jun;125(6):2473-83. (PMID: 25961453)
J Immunol. 2008 Feb 1;180(3):1903-12. (PMID: 18209088)
Semin Nephrol. 2012 May;32(3):228-35. (PMID: 22835453)
Am J Pathol. 2009 Oct;175(4):1371-3. (PMID: 19729485)
Kidney Blood Press Res. 1998;21(1):1-12. (PMID: 9661131)
Ann Rheum Dis. 2012 Feb;71(2):295-301. (PMID: 21979002)
Mediators Inflamm. 2015;2015:437695. (PMID: 25878399)
Genes Dev. 2000 Jan 15;14(2):187-97. (PMID: 10652273)
Cold Spring Harb Perspect Biol. 2018 Apr 2;10(4):. (PMID: 28432134)
Exp Cell Res. 2003 Jan 15;282(2):90-100. (PMID: 12531695)
Annu Rev Immunol. 2006;24:99-146. (PMID: 16551245)
Clin Exp Rheumatol. 2018 May-Jun;36 Suppl 112(3):80-88. (PMID: 29148407)
J Am Soc Nephrol. 2004 Jan;15(1):1-12. (PMID: 14694152)
J Clin Invest. 2004 Nov;114(9):1308-16. (PMID: 15520863)
Arthritis Rheum. 2003 Apr;48(4):1071-9. (PMID: 12687551)
J Cell Biol. 2002 Jan 21;156(2):299-313. (PMID: 11790801)
Ann Rheum Dis. 1997 Jul;56(7):426-31. (PMID: 9486005)
J Clin Invest. 2009 Jun;119(6):1417-9. (PMID: 19487817)
Lab Invest. 1994 May;70(5):620-30. (PMID: 8196359)
EMBO Mol Med. 2009 Sep;1(6-7):303-14. (PMID: 20049734)
J Am Soc Nephrol. 2009 Mar;20(3):567-81. (PMID: 19193779)
Clin Exp Immunol. 2002 Mar;127(3):547-52. (PMID: 11966774)
J Rheumatol. 2005 Aug;32(8):1440-7. (PMID: 16078317)
Lab Invest. 2010 Apr;90(4):543-55. (PMID: 20142803)
Cell Mol Biol Lett. 2007 Sep;12(3):457-72. (PMID: 17457524)
Nat Med. 2012 Jul 06;18(7):1028-40. (PMID: 22772564)
Biochem Biophys Res Commun. 2002 Sep 6;296(5):1356-65. (PMID: 12207925)
Histol Histopathol. 2011 Jan;26(1):107-16. (PMID: 21117032)
Oncogene. 2005 Aug 29;24(37):5764-74. (PMID: 16123809)
Biochim Biophys Acta. 2009 Aug;1792(8):746-56. (PMID: 19539753)

Keywords: TGF-β; autoimmune diseases; epithelial-mesenchymal transition; fibrosis; inflammation

0 (Transforming Growth Factor beta)

Date Created: 20210306 Date Completed: 20210723 Latest Revision: 20210723

20221213

PMC7922523

10.3390/biom11020310

33670735