title: Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting.
abstract: MicroRNAs (miRNAs) belong to a group of short noncoding RNA molecules with important roles in cellular biology. miRNAs regulate gene expression by repressing translation or degrading the target mRNA. Recently, a growing body of evidence suggests that miRNAs are implicated in many diseases and could be potential biomarkers. Fibrosis and/smooth muscle (SM) dysfunction contributes to the morbidity and mortality associated with several diseases of the gastrointestinal tract (GIT). Currently available therapeutic modalities are unsuccessful in efficiently blocking or reversing fibrosis and/or SM dysfunction. Recent understanding of the role of miRNAs in signaling pathway of fibrogenesis and SM phenotype switch has provided a new insight into translational research. However, much is still unknown about the molecular targets and therapeutic potential of miRNAs in the GIT. This review discusses miRNA biology, pathophysiology of fibrosis, and aging- associated SM dysfunction in relation to the deregulation of miRNAs in the GIT. We also highlight the role of selected miRNAs associated with fibrosis and SM dysfunction-related diseases of the GIT.
authors.affiliation: Department of Dermatology, Pondicherry Institute of Medical Sciences, Puducherry, India;
authors.forename: Chadalavada Vijay
authors.initials: CV
authors.lastname: Krishna
authors.affiliation: Department of Medicine, Division of Gastroenterology & Hepatology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; and.
authors.forename: Jagmohan
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Cancer Center (TC), Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Chellappagounder
authors.initials: C
authors.lastname: Thangavel
authors.affiliation: Department of Medicine, Division of Gastroenterology & Hepatology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; and.
authors.forename: Satish
authors.initials: S
authors.lastname: Rattan
mesh_terms: D000367:Age Factors; D000818:Animals; D044127:Epigenesis, Genetic; D005355:Fibrosis; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: cellular and epigenetic mechanisms; inflammatory mediators; microRNA; phenotypic plasticity; rho kinase; smooth muscle fibrosis; smooth muscle phenotypic switch
references.citation: Wiley Interdiscip Rev RNA. 2016 Mar;7(2):148-56
references.pmid: 26670867
references.citation: Dis Colon Rectum. 2007 Sep;50(9):1405-11
references.pmid: 17665265
references.citation: Oxid Med Cell Longev. 2015;2015:792846
references.pmid: 25815108
references.citation: J Investig Dermatol Symp Proc. 2006 Sep;11(1):66-72
references.pmid: 17069012
references.citation: EMBO Rep. 2012 Aug;13(8):716-23
references.pmid: 22677978
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D202-9
references.pmid: 21037263
references.citation: Eur Neuropsychopharmacol. 2016 Jan;26(1):23-36
references.pmid: 26628105
references.citation: Curr Opin Gastroenterol. 2008 Jul;24(4):462-8
references.pmid: 18622160
references.citation: J Rheumatol. 2015 Feb;42(2):214-21
references.pmid: 25399392
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references.pmid: 18158296
references.citation: Mol Cell. 2015 Jul 16;59(2):217-28
references.pmid: 26145174
references.citation: Stem Cells Int. 2014;2014:340257
references.pmid: 25132856
references.citation: Cell. 2005 Nov 18;123(4):621-9
references.pmid: 16271385
references.citation: Sci Signal. 2014 Sep 23;7(344):re8
references.pmid: 25249658
references.citation: Science. 2001 Aug 3;293(5531):834-8
references.pmid: 11452083
references.citation: Heredity (Edinb). 2016 Feb;116(2):125-34
references.pmid: 26419338
references.citation: Adv Exp Med Biol. 2015;888:71-83
references.pmid: 26663179
references.citation: J Cell Biol. 2011 Apr 18;193(2):409-24
references.pmid: 21502362
references.citation: Int J Mol Med. 2012 Apr;29(4):601-6
references.pmid: 22294131
references.citation: Cell. 2007 Jul 13;130(1):89-100
references.pmid: 17599402
references.citation: Rheumatology (Oxford). 2012 Sep;51(9):1550-6
references.pmid: 22661558
references.citation: Mod Pathol. 1991 Jan;4(1):87-90
references.pmid: 2020666
references.citation: Nature. 2003 Sep 25;425(6956):415-9
references.pmid: 14508493
references.citation: Physiol Genomics. 2011 May 1;43(10):621-30
references.pmid: 20841498
references.citation: Aging Cell. 2010 Apr;9(2):291-6
references.pmid: 20089119
references.citation: Int J Biol Sci. 2012;8(2):171-86
references.pmid: 22211115
references.citation: Gastroenterology. 2012 Sep;143(3):687-97.e1-9
references.pmid: 22683258
references.citation: Am J Physiol Cell Physiol. 2014 Dec 15;307(12):C1093-101
references.pmid: 25273883
references.citation: Nat Rev Gastroenterol Hepatol. 2009 Apr;6(4):228-35
references.pmid: 19347014
references.citation: Clin Chem. 2014 Sep;60(9):1200-8
references.pmid: 24987111
references.citation: Hepatology. 2010 Jan;51(1):267-76
references.pmid: 19827165
references.citation: Clin Chem. 2011 Jun;57(6):833-40
references.pmid: 21487102
references.citation: Mol Ther. 2012 Jun;20(6):1251-60
references.pmid: 22395530
references.citation: N Engl J Med. 2001 Feb 8;344(6):418-23
references.pmid: 11172178
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: J Cell Biol. 2006 Mar 27;172(7):973-81
references.pmid: 16567498
references.citation: Biology (Basel). 2013 Jan 25;2(1):189-205
references.pmid: 24832658
references.citation: Cell Res. 2008 Oct;18(10):997-1006
references.pmid: 18766170
references.citation: PLoS One. 2011;6(4):e18628
references.pmid: 21533178
references.citation: Curr Rheumatol Rep. 2015 Jan;17(1):474
references.pmid: 25604573
references.citation: Am J Physiol Gastrointest Liver Physiol. 2014 Jun 1;306(11):G983-91
references.pmid: 24742984
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Circ Res. 2009 Feb 27;104(4):476-87
references.pmid: 19150885
references.citation: Nature. 2004 Sep 16;431(7006):350-5
references.pmid: 15372042
references.citation: J Pathol. 2003 Jul;200(4):500-3
references.pmid: 12845617
references.citation: Sci Rep. 2015;5:17762
references.pmid: 26643997
references.citation: PLoS One. 2011;6(9):e24568
references.pmid: 21931759
references.citation: RNA. 2006 Feb;12(2):192-7
references.pmid: 16373484
references.citation: Ageing Res Rev. 2014 Nov;18:132-47
references.pmid: 25311590
references.citation: BMC Genomics. 2007;8:166
references.pmid: 17565689
references.citation: Inflamm Bowel Dis. 2014 Nov;20(11):2198-206
references.pmid: 24892966
references.citation: J Dermatol Sci. 2011 Jan;61(1):67-9
references.pmid: 21129921
references.citation: Genome Res. 2015 Feb;25(2):257-67
references.pmid: 25378249
references.citation: Diabetes. 2011 Jan;60(1):280-7
references.pmid: 20952520
references.citation: Gastroenterology. 2010 Jan;138(1):13-8.e1-3
references.pmid: 19931260
references.citation: Cell Death Dis. 2015;6:e2011
references.pmid: 26633717
references.citation: Nat Rev Cancer. 2011 Jan;11(1):59-67
references.pmid: 21160526
references.citation: Molecules. 2014;19(10):15611-23
references.pmid: 25268717
references.citation: Nat Rev Genet. 2011 Feb;12(2):99-110
references.pmid: 21245828
references.citation: Rheumatology (Oxford). 2015 Nov;54(11):2100-7
references.pmid: 26163687
references.citation: J Clin Invest. 2005 Feb;115(2):209-18
references.pmid: 15690074
references.citation: J Immunol. 2012 Apr 1;188(7):3323-31
references.pmid: 22379029
references.citation: Expert Opin Ther Targets. 2012 Sep;16(9):875-9
references.pmid: 22793265
references.citation: J Cutan Pathol. 2004 Jul;31(6):431-40
references.pmid: 15186431
references.citation: Kidney Int. 2002 May;61(5):1684-95
references.pmid: 11967018
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G664-75
references.pmid: 22241857
references.citation: Eur Heart J. 2010 Mar;31(6):659-66
references.pmid: 20159880
references.citation: Tumour Biol. 2016 Jun;37(6):7777-84
references.pmid: 26695145
references.citation: Am J Pathol. 2013 Jan;182(1):192-205
references.pmid: 23141927
references.citation: Am J Physiol Gastrointest Liver Physiol. 2015 May 15;308(10):G807-30
references.pmid: 25767261
references.citation: Arthritis Rheum. 2010 Jun;62(6):1733-43
references.pmid: 20201077
references.citation: Gastroenterology. 2014 Feb;146(2):473-83.e3
references.pmid: 24507550
references.citation: PLoS One. 2015;10(12):e0145930
references.pmid: 26720041
references.citation: Autoimmun Rev. 2003 Jun;2(4):181-91
references.pmid: 12848944
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: J Pediatr Surg. 2008 Jun;43(6):1106-10
references.pmid: 18558191
references.citation: Nature. 2008 Sep 4;455(7209):64-71
references.pmid: 18668037
references.citation: Nat Cell Biol. 2008 May;10(5):593-601
references.pmid: 18376396
references.citation: Annu Rev Physiol. 2006;68:345-74
references.pmid: 16460276
references.citation: Int J Biochem Cell Biol. 2010 Jun;42(6):828-43
references.pmid: 19944184
references.citation: PLoS One. 2008;3(9):e3220
references.pmid: 18795102
references.citation: Nat Biotechnol. 2011 Apr;29(4):341-5
references.pmid: 21423189
references.citation: Gut. 2004 Jul;53(7):987-92
references.pmid: 15194649
references.citation: Cell. 2005 Aug 26;122(4):553-63
references.pmid: 16122423
references.citation: J Am Soc Hypertens. 2015 Mar;9(3):221-34
references.pmid: 25660363
references.citation: Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):368-75
references.pmid: 21051663
references.citation: Mamm Genome. 2009 Sep-Oct;20(9-10):581-603
references.pmid: 19876605
references.citation: Nucleic Acids Res. 2015 Jul 1;43(W1):W480-6
references.pmid: 25990732
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Drug Dev Res. 2015 Nov;76(7):389-96
references.pmid: 26286669
references.citation: Genes Dev. 2003 Dec 15;17(24):3011-6
references.pmid: 14681208
references.citation: N Engl J Med. 2009 May 7;360(19):1989-2003
references.pmid: 19420368
references.citation: J Cell Mol Med. 2015 Jan;19(1):62-73
references.pmid: 25283476
references.citation: Am J Physiol Cell Physiol. 2007 Jan;292(1):C70-81
references.pmid: 16928770
references.citation: J Immunol. 2013 Apr 15;190(8):3905-15
references.pmid: 23509348
references.citation: Gene. 2014 Jul 10;544(2):259-60
references.pmid: 24792894
references.citation: J Biol Chem. 2016 Feb 12;291(7):3552-68
references.pmid: 26683376
references.citation: Am J Pathol. 2011 Nov;179(5):2660-73
references.pmid: 21945322
references.citation: Clin Chem. 2010 Nov;56(11):1733-41
references.pmid: 20847327
references.citation: Am J Pathol. 2007 Jun;170(6):1807-16
references.pmid: 17525249
references.citation: Arthritis Res Ther. 2005;7(5):R1113-23
references.pmid: 16207328
references.citation: J Biol Chem. 2009 Feb 6;284(6):3728-38
references.pmid: 19088079
references.citation: Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):195-206
references.pmid: 21497738
references.citation: Nat Rev Gastroenterol Hepatol. 2012 Nov;9(11):633-45
references.pmid: 22965426
references.citation: Am J Respir Crit Care Med. 2014 Dec 1;190(11):1263-72
references.pmid: 25333685
references.citation: IUBMB Life. 2015 Dec;67(12):923-7
references.pmid: 26602058
references.citation: Inflamm Bowel Dis. 2015 Aug;21(8):1926-34
references.pmid: 25985247
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: Genes Dev. 2004 Dec 15;18(24):3016-27
references.pmid: 15574589
references.citation: J Clin Immunol. 2012 Jun;32(3):514-22
references.pmid: 22307526
references.citation: Dig Dis Sci. 2015 Aug;60(8):2304-15
references.pmid: 25749934
references.citation: Science. 2012 Apr 13;336(6078):237-40
references.pmid: 22499947
references.citation: Am J Physiol Gastrointest Liver Physiol. 2015 Jun 1;308(11):G924-33
references.pmid: 25882611
references.citation: Biochimie. 2013 Jul;95(7):1355-9
references.pmid: 23542596
references.citation: Nat Genet. 2005 Jul;37(7):766-70
references.pmid: 15965474
references.citation: Biomarkers. 2016 Mar;21(2):129-37
references.pmid: 26631297
references.citation: PLoS One. 2014;9(5):e96338
references.pmid: 24848371
references.citation: Gastroenterology. 2006 Jul;131(1):108-16
references.pmid: 16831595
references.citation: Biochem Biophys Res Commun. 2011 Aug 19;412(1):74-9
references.pmid: 21798245
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Physiol Rev. 2004 Jul;84(3):767-801
references.pmid: 15269336
references.citation: Cardiovasc Res. 2012 Nov 1;96(2):320-9
references.pmid: 22871591
references.citation: EXS. 2015;106:171-95
references.pmid: 26608204
references.citation: Front Cell Infect Microbiol. 2012;2:137
references.pmid: 23130352
references.citation: J Cell Physiol. 2016 Feb;231(2):295-302
references.pmid: 26206426
references.citation: J Pathol. 2008 Jan;214(2):199-210
references.pmid: 18161745
references.citation: J Cell Mol Med. 2015 Mar;19(3):511-20
references.pmid: 25534251
references.citation: J Biol Chem. 2010 Jun 25;285(26):20202-12
references.pmid: 20363741
references.citation: Clin Sci (Lond). 2014 Sep;127(5):341-50
references.pmid: 24641356
references.citation: Gastroenterology. 2004 Apr;126(4):955-63
references.pmid: 15057733
references.citation: Nature. 2001 Jan 18;409(6818):363-6
references.pmid: 11201747
references.citation: Nature. 2009 Aug 6;460(7256):705-10
references.pmid: 19578358
references.citation: RNA. 2005 Dec;11(12):1753-61
references.pmid: 16314451
references.citation: J Biomed Inform. 2011 Oct;44(5):839-47
references.pmid: 21605702
references.citation: Adv Exp Med Biol. 2015;888:253-69
references.pmid: 26663187
references.citation: Gastroenterology. 2011 Jul;141(1):164-75
references.pmid: 21473868
references.citation: J Pharmacol Sci. 2010;114(3):264-8
references.pmid: 20953121