#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Disruption of miR-29 Leads to Aberrant Differentiation of Smooth Muscle Cells Selectively Associated with Distal Lung Vasculature


The pathogenesis of some vascular diseases, such as PAH is selectively associated with aberrant differentiation and proliferation of vSMCs of distal arteries. While significant progresses have been made in understanding the core mechanism of differentiation and proliferation of vSMCs, little is known regarding vessel specific regulations. By investigating the expression and function of miR-29 in vivo, we found a vessel selective enriched expression and function of miR-29 during mouse lung development. Interestingly, disruption of miR-29 results in defects in vSMCs differentiation of distal vessels, reminiscent of vSMC phenotype observed in the early stage of PAH in which immature/synthetic vSMCs of distal arteries failed to differentiate and were unable to tune down the expression of collagens and other extracellular-related genes. This is the first evidence that miR-29 selectively regulates vSMCs differentiation and vessel wall formation. Future implications are to study the expression and function of miR-29 in human pulmonary vascular diseases, which might lead to establishing miR-29 as a therapeutic target for disease intervention.


Vyšlo v časopise: Disruption of miR-29 Leads to Aberrant Differentiation of Smooth Muscle Cells Selectively Associated with Distal Lung Vasculature. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005238
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005238

Souhrn

The pathogenesis of some vascular diseases, such as PAH is selectively associated with aberrant differentiation and proliferation of vSMCs of distal arteries. While significant progresses have been made in understanding the core mechanism of differentiation and proliferation of vSMCs, little is known regarding vessel specific regulations. By investigating the expression and function of miR-29 in vivo, we found a vessel selective enriched expression and function of miR-29 during mouse lung development. Interestingly, disruption of miR-29 results in defects in vSMCs differentiation of distal vessels, reminiscent of vSMC phenotype observed in the early stage of PAH in which immature/synthetic vSMCs of distal arteries failed to differentiate and were unable to tune down the expression of collagens and other extracellular-related genes. This is the first evidence that miR-29 selectively regulates vSMCs differentiation and vessel wall formation. Future implications are to study the expression and function of miR-29 in human pulmonary vascular diseases, which might lead to establishing miR-29 as a therapeutic target for disease intervention.


Zdroje

1. Stenmark KR, Abman SH (2005) Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol 67: 623–661. 15709973

2. Owens GK (2007) Molecular control of vascular smooth muscle cell differentiation and phenotypic plasticity. Novartis Found Symp 283: 174–191; discussion 191–173, 238–141. 18300422

3. Haworth SG (1995) Development of the normal and hypertensive pulmonary vasculature. Exp Physiol 80: 843–853. 8546873

4. Hall SM, Gorenflo M, Reader J, Lawson D, Haworth SG (2000) Neonatal pulmonary hypertension prevents reorganisation of the pulmonary arterial smooth muscle cytoskeleton after birth. J Anat 196 (Pt 3): 391–403. 10853961

5. Zhou W, Dasgupta C, Negash S, Raj JU (2007) Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of cGMP-dependent protein kinase. Am J Physiol Lung Cell Mol Physiol 292: L1459–1466. 17322285

6. Morrell NW, Adnot S, Archer SL, Dupuis J, Jones PL, et al. (2009) Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol 54: S20–31. doi: 10.1016/j.jacc.2009.04.018 19555855

7. Tuder RM, Stacher E, Robinson J, Kumar R, Graham BB (2013) Pathology of pulmonary hypertension. Clin Chest Med 34: 639–650. doi: 10.1016/j.ccm.2013.08.009 24267295

8. Tuder RM, Abman SH, Braun T, Capron F, Stevens T, et al. (2009) Development and pathology of pulmonary hypertension. J Am Coll Cardiol 54: S3–9. doi: 10.1016/j.jacc.2009.04.009 19555856

9. Farber HW, Loscalzo J (2004) Pulmonary arterial hypertension. N Engl J Med 351: 1655–1665. 15483284

10. Suzuki T, Aizawa K, Matsumura T, Nagai R (2005) Vascular implications of the Kruppel-like family of transcription factors. Arterioscler Thromb Vasc Biol 25: 1135–1141. 15817882

11. Wang DZ, Olson EN (2004) Control of smooth muscle development by the myocardin family of transcriptional coactivators. Curr Opin Genet Dev 14: 558–566. 15380248

12. Hughes AD, Clunn GF, Refson J, Demoliou-Mason C (1996) Platelet-derived growth factor (PDGF): actions and mechanisms in vascular smooth muscle. Gen Pharmacol 27: 1079–1089. 8981052

13. Hellberg C, Ostman A, Heldin CH (2010) PDGF and vessel maturation. Recent Results Cancer Res 180: 103–114. doi: 10.1007/978-3-540-78281-0_7 20033380

14. Rabinovitch M (2012) Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 122: 4306–4313. doi: 10.1172/JCI60658 23202738

15. West J (2010) Cross talk between Smad, MAPK, and actin in the etiology of pulmonary arterial hypertension. Adv Exp Med Biol 661: 265–278. doi: 10.1007/978-1-60761-500-2_17 20204736

16. Lagna G, Nguyen PH, Ni W, Hata A (2006) BMP-dependent activation of caspase-9 and caspase-8 mediates apoptosis in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 291: L1059–1067. 17030903

17. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233. doi: 10.1016/j.cell.2009.01.002 19167326

18. Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernandez-Hernando C, et al. (2011) Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. PLoS One 6: e18869. doi: 10.1371/journal.pone.0018869 21526127

19. Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, et al. (2010) MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol 30: 1118–1126. doi: 10.1161/ATVBAHA.109.200873 20378849

20. Xin M, Small EM, Sutherland LB, Qi X, McAnally J, et al. (2009) MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev 23: 2166–2178. doi: 10.1101/gad.1842409 19720868

21. Paez-Cortez J, Krishnan R, Arno A, Aven L, Ram-Mohan S, et al. (2013) A new approach for the study of lung smooth muscle phenotypes and its application in a murine model of allergic airway inflammation. PLoS One 8: e74469. doi: 10.1371/journal.pone.0074469 24040256

22. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, et al. (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 105: 13027–13032. doi: 10.1073/pnas.0805038105 18723672

23. Cushing L, Kuang PP, Qian J, Shao F, Wu J, et al. (2011) miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol 45: 287–294. doi: 10.1165/rcmb.2010-0323OC 20971881

24. Ehler E, Babiychuk E, Draeger A (1996) Human foetal lung (IMR-90) cells: myofibroblasts with smooth muscle-like contractile properties. Cell Motil Cytoskeleton 34: 288–298. 8871816

25. Liu Y, Sinha S, McDonald OG, Shang Y, Hoofnagle MH, et al. (2005) Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression. J Biol Chem 280: 9719–9727. 15623517

26. Chen CN, Li YS, Yeh YT, Lee PL, Usami S, et al. (2006) Synergistic roles of platelet-derived growth factor-BB and interleukin-1beta in phenotypic modulation of human aortic smooth muscle cells. Proc Natl Acad Sci U S A 103: 2665–2670. 16477012

27. Stamatiou R, Paraskeva E, Gourgoulianis K, Molyvdas PA, Hatziefthimiou A (2012) Cytokines and growth factors promote airway smooth muscle cell proliferation. ISRN Inflamm 2012: 731472. doi: 10.5402/2012/731472 24049651

28. Kawai-Kowase K, Owens GK (2007) Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells. Am J Physiol Cell Physiol 292: C59–69. 16956962

29. Maurer B, Stanczyk J, Jungel A, Akhmetshina A, Trenkmann M, et al. (2010) MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 62: 1733–1743. doi: 10.1002/art.27443 20201077

30. Sekiya Y, Ogawa T, Yoshizato K, Ikeda K, Kawada N (2011) Suppression of hepatic stellate cell activation by microRNA-29b. Biochem Biophys Res Commun 412: 74–79. doi: 10.1016/j.bbrc.2011.07.041 21798245

31. Kwiecinski M, Elfimova N, Noetel A, Tox U, Steffen HM, et al. (2012) Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29. Lab Invest 92: 978–987. doi: 10.1038/labinvest.2012.70 22565577

32. Talasila A, Yu H, Ackers-Johnson M, Bot M, van Berkel T, et al. (2013) Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-beta. Arterioscler Thromb Vasc Biol 33: 2355–2365. doi: 10.1161/ATVBAHA.112.301000 23825366

33. Glass DJ (2003) Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 5: 87–90. 12563267

34. Bodine SC, Baehr LM (2014) Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab 307: E469–484. doi: 10.1152/ajpendo.00204.2014 25096180

35. Lu T, Chai Q, Yu L, d'Uscio LV, Katusic ZS, et al. (2012) Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel beta1 subunit degradation in diabetic mice. Diabetes 61: 1860–1868. doi: 10.2337/db11-1658 22586590

36. Yi F, Wang H, Chai Q, Wang X, Shen WK, et al. (2014) Regulation of large conductance Ca2+-activated K+ (BK) channel beta1 subunit expression by muscle RING finger protein 1 in diabetic vessels. J Biol Chem 289: 10853–10864. doi: 10.1074/jbc.M113.520940 24570002

37. Zhang DM, He T, Katusic ZS, Lee HC, Lu T (2010) Muscle-specific f-box only proteins facilitate bk channel beta(1) subunit downregulation in vascular smooth muscle cells of diabetes mellitus. Circ Res 107: 1454–1459. doi: 10.1161/CIRCRESAHA.110.228361 20966391

38. Tucka J, Yu H, Gray K, Figg N, Maguire J, et al. (2014) Akt1 regulates vascular smooth muscle cell apoptosis through FoxO3a and Apaf1 and protects against arterial remodeling and atherosclerosis. Arterioscler Thromb Vasc Biol 34: 2421–2428. doi: 10.1161/ATVBAHA.114.304284 25234814

39. Lee HY, Chung JW, Youn SW, Kim JY, Park KW, et al. (2007) Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res 100: 372–380. 17234971

40. Allard D, Figg N, Bennett MR, Littlewood TD (2008) Akt regulates the survival of vascular smooth muscle cells via inhibition of FoxO3a and GSK3. J Biol Chem 283: 19739–19747. doi: 10.1074/jbc.M710098200 18458087

41. Guerit D, Brondello JM, Chuchana P, Philipot D, Toupet K, et al. (2014) FOXO3A regulation by miRNA-29a Controls chondrogenic differentiation of mesenchymal stem cells and cartilage formation. Stem Cells Dev 23: 1195–1205. doi: 10.1089/scd.2013.0463 24467486

42. Liston A, Papadopoulou AS, Danso-Abeam D, Dooley J (2012) MicroRNA-29 in the adaptive immune system: setting the threshold. Cell Mol Life Sci 69: 3533–3541. doi: 10.1007/s00018-012-1124-0 22971773

43. He Y, Huang C, Lin X, Li J (2013) MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases. Biochimie 95: 1355–1359. doi: 10.1016/j.biochi.2013.03.010 23542596

44. Wang Y, Zhang X, Li H, Yu J, Ren X (2013) The role of miRNA-29 family in cancer. Eur J Cell Biol 92: 123–128. doi: 10.1016/j.ejcb.2012.11.004 23357522

45. Pekarsky Y, Croce CM (2010) Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget 1: 224–227. 20936047

46. Montgomery RL, Yu G, Latimer PA, Stack C, Robinson K, et al. (2014) MicroRNA mimicry blocks pulmonary fibrosis. EMBO Mol Med 6: 1347–1356. doi: 10.15252/emmm.201303604 25239947

47. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, et al. (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104: 15805–15810. 17890317

48. Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, et al. (2009) MicroRNA 29b functions in acute myeloid leukemia. Blood 114: 5331–5341. doi: 10.1182/blood-2009-03-211938 19850741

49. Kogure T, Costinean S, Yan I, Braconi C, Croce C, et al. (2012) Hepatic miR-29ab1 expression modulates chronic hepatic injury. J Cell Mol Med 16: 2647–2654. doi: 10.1111/j.1582-4934.2012.01578.x 22469499

50. Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, et al. (2009) Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284: 15676–15684. doi: 10.1074/jbc.M809787200 19342382

51. Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, et al. (2006) Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66: 11590–11593. 17178851

52. Santanam U, Zanesi N, Efanov A, Costinean S, Palamarchuk A, et al. (2010) Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A 107: 12210–12215. doi: 10.1073/pnas.1007186107 20566844

53. Smith KM, Guerau-de-Arellano M, Costinean S, Williams JL, Bottoni A, et al. (2012) miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. J Immunol 189: 1567–1576. doi: 10.4049/jimmunol.1103171 22772450

54. Wang H, Garzon R, Sun H, Ladner KJ, Singh R, et al. (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14: 369–381. doi: 10.1016/j.ccr.2008.10.006 18977326

55. Ott CE, Grunhagen J, Jager M, Horbelt D, Schwill S, et al. (2011) MicroRNAs differentially expressed in postnatal aortic development downregulate elastin via 3' UTR and coding-sequence binding sites. PLoS One 6: e16250. doi: 10.1371/journal.pone.0016250 21305018

56. Wei W, He HB, Zhang WY, Zhang HX, Bai JB, et al. (2013) miR-29 targets Akt3 to reduce proliferation and facilitate differentiation of myoblasts in skeletal muscle development. Cell Death Dis 4: e668. doi: 10.1038/cddis.2013.184 23764849

57. Ma W, Xie S, Ni M, Huang X, Hu S, et al. (2012) MicroRNA-29a inhibited epididymal epithelial cell proliferation by targeting nuclear autoantigenic sperm protein (NASP). J Biol Chem 287: 10189–10199. doi: 10.1074/jbc.M111.303636 22194605

58. Podolska A, Kaczkowski B, Kamp Busk P, Sokilde R, Litman T, et al. (2011) MicroRNA expression profiling of the porcine developing brain. PLoS One 6: e14494. doi: 10.1371/journal.pone.0014494 21253018

59. Li Y, Piatigorsky J (2009) Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development. Dev Dyn 238: 2388–2400. doi: 10.1002/dvdy.22056 19681134

60. Wang L, Zhou L, Jiang P, Lu L, Chen X, et al. (2012) Loss of miR-29 in myoblasts contributes to dystrophic muscle pathogenesis. Mol Ther 20: 1222–1233. doi: 10.1038/mt.2012.35 22434133

61. Boettger T, Beetz N, Kostin S, Schneider J, Kruger M, et al. (2009) Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 119: 2634–2647. doi: 10.1172/JCI38864 19690389

62. Chen Z, Wu J, Yang C, Fan P, Balazs L, et al. (2012) DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. J Biol Chem 287: 19018–19028. doi: 10.1074/jbc.M112.351791 22511778

63. Fan P, Chen Z, Tian P, Liu W, Jiao Y, et al. (2013) miRNA biogenesis enzyme Drosha is required for vascular smooth muscle cell survival. PLoS One 8: e60888. doi: 10.1371/journal.pone.0060888 23637774

64. Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, et al. (2009) The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 16: 1590–1598. doi: 10.1038/cdd.2009.153 19816508

65. Cittelly DM, Finlay-Schultz J, Howe EN, Spoelstra NS, Axlund SD, et al. (2013) Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4. Oncogene 32: 2555–2564. doi: 10.1038/onc.2012.275 22751119

66. Tang W, Zhu Y, Gao J, Fu J, Liu C, et al. (2014) MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4. Br J Cancer 110: 450–458. doi: 10.1038/bjc.2013.724 24281002

67. Turner EC, Huang CL, Govindarajan K, Caplice NM (2013) Identification of a Klf4-dependent upstream repressor region mediating transcriptional regulation of the myocardin gene in human smooth muscle cells. Biochim Biophys Acta 1829: 1191–1201. doi: 10.1016/j.bbagrm.2013.09.002 24060351

68. Cushing L, Kuang P, Lu J (2015) The role of miR-29 in pulmonary fibrosis. Biochem Cell Biol 93: 109–118. doi: 10.1139/bcb-2014-0095 25454218

69. Caruso P, Dempsie Y, Stevens HC, McDonald RA, Long L, et al. (2012) A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples. Circ Res 111: 290–300. doi: 10.1161/CIRCRESAHA.112.267591 22715469

70. Wohrley JD, Frid MG, Moiseeva EP, Orton EC, Belknap JK, et al. (1995) Hypoxia selectively induces proliferation in a specific subpopulation of smooth muscle cells in the bovine neonatal pulmonary arterial media. J Clin Invest 96: 273–281. 7615796

71. Prosser IW, Stenmark KR, Suthar M, Crouch EC, Mecham RP, et al. (1989) Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am J Pathol 135: 1073–1088. 2596571

72. Stenmark KR, Orton EC, Reeves JT, Voelkel NF, Crouch EC, et al. (1988) Vascular remodeling in neonatal pulmonary hypertension. Role of the smooth muscle cell. Chest 93: 127S–133S. 3342691

73. Davis-Dusenbery BN, Chan MC, Reno KE, Weisman AS, Layne MD, et al. (2011) down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4. J Biol Chem 286: 28097–28110. doi: 10.1074/jbc.M111.236950 21673106

74. Mam V, Tanbe AF, Vitali SH, Arons E, Christou HA, et al. (2010) Impaired vasoconstriction and nitric oxide-mediated relaxation in pulmonary arteries of hypoxia- and monocrotaline-induced pulmonary hypertensive rats. J Pharmacol Exp Ther 332: 455–462. doi: 10.1124/jpet.109.160119 19915069

75. Qiao L, Xie L, Shi K, Zhou T, Hua Y, et al. (2012) Notch signaling change in pulmonary vascular remodeling in rats with pulmonary hypertension and its implication for therapeutic intervention. PLoS One 7: e51514. doi: 10.1371/journal.pone.0051514 23251561

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#