Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The effects of miRNA-145 on the phenotypic modulation of rat corpus cavernosum smooth muscle cells

Abstract

To investigate the effect of miR-145 on the phenotypic modulation in rat corpus cavernosum smooth muscle cells. Corpus cavernosum smooth muscle cells were treated with either miR-145 mimics or miR-145 negative control. Cell proliferation were analyzed by the MTS assay and colony formation assay. Wound healing assay were performed to detect the effect of miR-145 on cell migration. The mRNA and protein levels of phenotype marker proteins were assessed by quantitative real-time polymerase chain reaction and western blotting. The intracavernosal pressure and mean arterial pressure were measured to assess erectile function at one month after the injection of platelet-derived growth factor-BB and miR-145. Our results showed that miR-145 inhibited the proliferation and migration of cavernosal smooth muscle cells. Smooth muscle cell phenotypic markers were also affected by overexpression of miR-145, as indicated by the increase in α-smooth muscle actin, calponin and smooth muscle myosin heavy chain expression. Moreover, significantly attenuated erectile function was observed in the platelet-derived growth factor-BB group as compared with the platelet-derived growth factor-BB+miR-145 group. These findings indicated that miR-145 regulate phenotypic modulation of corpus cavernosum smooth muscle cells.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4

References

  1. 1

    Owens GK . Regulation of differentiation of vascular smooth muscle cells. Physiol Rev 1995; 75: 487–517.

    CAS  Article  Google Scholar 

  2. 2

    Rensen SS, Doevendans PA, van Eys GJ . Regulation and characteristics of vascular smooth muscle cell phenotypic diversity. Neth Heart J 2007; 15: 100–108.

    CAS  Article  Google Scholar 

  3. 3

    Beamish JA, He P, Kottke-Marchant K, Marchant RE . Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng B Rev 2010; 16: 467–491.

    CAS  Article  Google Scholar 

  4. 4

    Owens GK, Kumar MS, Wamhoff BR . Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004; 84: 767–801.

    CAS  Article  Google Scholar 

  5. 5

    Libby P . Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32: 2045–2051.

    CAS  Article  Google Scholar 

  6. 6

    Prakash YS . Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol 2013; 305: L912–L933.

    CAS  Article  Google Scholar 

  7. 7

    Wei AY, He SH, Zhao JF, Liu Y, Liu Y, Hu YW et al. Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction. Int J Impot Res 2012; 24: 196–201.

    CAS  Article  Google Scholar 

  8. 8

    Luo JT, Huang ZS, Li H, Liu LH, Yu WJ, Zhang T et al. Phenotypic modulation of rat corpus cavernosum smooth muscle cells induced by platelet-derived growth factor-BB. Int J Clin Exp Pathol 2016; 9: 5087–5095.

    CAS  Google Scholar 

  9. 9

    Ambros V . The functions of animal microRNAs. Nature 2004; 431: 350–355.

    CAS  Article  Google Scholar 

  10. 10

    He L, Hannon GJ . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5: 522–531.

    CAS  Article  Google Scholar 

  11. 11

    Davis-Dusenbery BN, Wu C, Hata A . Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation. Arterioscler Thromb Vasc Biol 2011; 31: 2370–2377.

    CAS  Article  Google Scholar 

  12. 12

    Rangrez AY, Massy ZA, Metzinger-Le MV, Metzinger L . miR-143 and miR-145: molecular keys to switch the phenotype of vascular smooth muscle cells. Circ Cardiovasc Genet 2011; 4: 197–205.

    CAS  Article  Google Scholar 

  13. 13

    Pan F, Xu J, Zhang Q, Qiu X, Yu W, Xia J et al. Identification and characterization of the MicroRNA profile in aging rats with erectile dysfunction. J Sex Med 2014; 11: 1646–1656.

    CAS  Article  Google Scholar 

  14. 14

    Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 2007; 100: 1579–1588.

    CAS  Article  Google Scholar 

  15. 15

    Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 2009; 105: 158–166.

    CAS  Article  Google Scholar 

  16. 16

    He S, Zhang T, Liu Y, Liu L, Zhang H, Chen F et al. Myocardin restores erectile function in diabetic rats: phenotypic modulation of corpus cavernosum smooth muscle cells. Andrologia 2015; 47: 303–309.

    CAS  Article  Google Scholar 

  17. 17

    Zhao S, Liu L, Kang R, Li F, Li E, Zhang T et al. Shengjing Capsule Improves Erectile Function Through Regulation of Nitric Oxide-induced Relaxation in Corpus Cavernosum Smooth Muscle in a Castrated Rat Model. Urology 2016; 91: 243.e7–243.e12.

    Article  Google Scholar 

  18. 18

    Andrae J, Gallini R, Betsholtz C . Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008; 22: 1276–1312.

    CAS  Article  Google Scholar 

  19. 19

    Nehra A, Goldstein I, Pabby A, Nugent M, Huang YH, de Las MA et al. Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J Urol 1996; 156: 1320–1329.

    CAS  Article  Google Scholar 

  20. 20

    Lv B, Zhao J, Yang F, Huang X, Chen G, Yang K et al. Phenotypic transition of corpus cavernosum smooth muscle cells subjected to hypoxia. Cell Tissue Res 2014; 357: 823–833.

    Article  Google Scholar 

  21. 21

    Yang F, Zhao JF, Shou QY, Huang XJ, Chen G, Yang KB et al. Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy. PLoS ONE 2014; 9: e105186.

    Article  Google Scholar 

  22. 22

    Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF et al. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev 2009; 23: 2166–2178.

    CAS  Article  Google Scholar 

  23. 23

    Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 2009; 16: 1590–1598.

    CAS  Article  Google Scholar 

  24. 24

    Luttrell IP, Swee M, Starcher B, Parks WC, Chitaley K . Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix. Am J Physiol Heart Circ Physiol 2008; 294: H2204–H2211.

    CAS  Article  Google Scholar 

  25. 25

    Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009; 460: 705–710.

    CAS  Article  Google Scholar 

  26. 26

    Boettger T, Beetz N, Kostin S, Schneider J, Krüger M, Hein L et al. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 2009; 119: 2634–2647.

    CAS  Article  Google Scholar 

  27. 27

    Zhao N, Koenig SN, Trask AJ, Lin CH, Hans CP, Garg V et al. MicroRNA miR145 regulates TGFBR2 expression and matrix synthesis in vascular smooth musclecells. Circ Res 2015; 116: 23–34.

    CAS  Article  Google Scholar 

  28. 28

    Boucher JM, Peterson SM, Urs S, Zhang C, Liaw L . The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells. J Biol Chem 2011; 286: 28312–28321.

    CAS  Article  Google Scholar 

  29. 29

    Tang Y, Urs S, Liaw L . Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. Circ Res 2008; 102: 661–668.

    CAS  Article  Google Scholar 

  30. 30

    Gras C, Ratuszny D, Hadamitzky C, Zhang H, Blasczyk R, Figueiredo C . miR-145 Contributes to Hypertrophic Scarring of the Skin by Inducing Myofibroblast Activity. Mol Med 2015; 21: 296–304.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Natural Science Foundation of Guangdong Province. (2014A030313302) and National Natural Science Foundation of China (No. 81571433).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to A Wei or Z Zhao.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Luo, J., Liu, L., Wu, Z. et al. The effects of miRNA-145 on the phenotypic modulation of rat corpus cavernosum smooth muscle cells. Int J Impot Res 29, 229–234 (2017). https://doi.org/10.1038/ijir.2017.28

Download citation

Further reading

Search

Quick links