Anti-microRNA-378a Enhances Wound Healing Process by Upregulating Integrin Beta-3 and Vimentin

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2014 Jun 24

PMID 24954475

Citations 28

Authors

Haoran Li

Leslie Chang

William W Du

Shaan Gupta

Azam Khorshidi

Michael Sefton

Burton B Yang

Affiliations

Soon will be listed here.

Abstract

Delayed or impaired wound healing is a major public health issue worldwide, especially in patients with diabetes mellitus and vascular atherosclerosis. MicroRNAs have been identified as key regulators of wound healing. Here, we show that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p function) display enhanced wound healing. Expression of vimentin and β3 integrin, two important modulators of wound healing, is markedly elevated in the transgenic mice. MiR-Pirate378a-transfected cells display greater mobility during migration assays, which was hypothesized to be due to the upregulation of vimentin and β3 integrin. Both molecules were confirmed to be targets of miR-378a, and thus their expression could be rescued by miR-Pirate378a. Overexpression of vimentin also contributed to fibroblast differentiation, and upregulation of β3 integrin was responsible for increased angiogenesis. Mice treatment with miR-Pirate378a-conjugated nanoparticles displayed enhanced wound healing. Thus, we have demonstrated that knockdown of miR-378a increased the expression of its target proteins, vimentin, and β3 integrin, which accelerated fibroblast migration and differentiation in vitro and enhanced wound healing in vivo.

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References

Kahai S, Lee S, Lee D, Yang J, Li M, Wang C . MicroRNA miR-378 regulates nephronectin expression modulating osteoblast differentiation by targeting GalNT-7. PLoS One. 2009; 4(10):e7535. PMC: 2760121. DOI: 10.1371/journal.pone.0007535. View

Mahabeleshwar G, Chen J, Feng W, Somanath P, Razorenova O, Byzova T . Integrin affinity modulation in angiogenesis. Cell Cycle. 2008; 7(3):335-47. PMC: 2677212. DOI: 10.4161/cc.7.3.5234. View

Deng Z, Yang X, Fang L, Rutnam Z, Yang B . Misprocessing and functional arrest of microRNAs by miR-Pirate: roles of miR-378 and miR-17. Biochem J. 2012; 450(2):375-86. DOI: 10.1042/BJ20120722. View

Liu F, Lv Q, Du W, Li H, Yang X, Liu D . Specificity of miR-378a-5p targeting rodent fibronectin. Biochim Biophys Acta. 2013; 1833(12):3272-3285. DOI: 10.1016/j.bbamcr.2013.09.008. View

Babar I, Cheng C, Booth C, Liang X, Weidhaas J, Saltzman W . Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci U S A. 2012; 109(26):E1695-704. PMC: 3387084. DOI: 10.1073/pnas.1201516109. View

Biswas S, Roy S, Banerjee J, Hussain S, Khanna S, Meenakshisundaram G . Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. Proc Natl Acad Sci U S A. 2010; 107(15):6976-81. PMC: 2872456. DOI: 10.1073/pnas.1001653107. View

Sakamoto Y, Ogita H, Komura H, Takai Y . Involvement of nectin in inactivation of integrin alpha(v)beta(3) after the establishment of cell-cell adhesion. J Biol Chem. 2007; 283(1):496-505. DOI: 10.1074/jbc.M704195200. View

Green H, Kehinde O . An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell. 1975; 5(1):19-27. DOI: 10.1016/0092-8674(75)90087-2. View

Banerjee J, Sen C . MicroRNAs in skin and wound healing. Methods Mol Biol. 2012; 936:343-56. PMC: 4357320. DOI: 10.1007/978-1-62703-083-0_26. View

10.

Shu Y, Maibach H . Estrogen and skin: therapeutic options. Am J Clin Dermatol. 2011; 12(5):297-311. DOI: 10.2165/11589180-000000000-00000. View

11.

Rutnam Z, Du W, Yang W, Yang X, Yang B . The pseudogene TUSC2P promotes TUSC2 function by binding multiple microRNAs. Nat Commun. 2014; 5:2914. PMC: 3896787. DOI: 10.1038/ncomms3914. View

12.

Boutla A, Delidakis C, Tabler M . Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Nucleic Acids Res. 2003; 31(17):4973-80. PMC: 212806. DOI: 10.1093/nar/gkg707. View

13.

Hong H, Jin S, Park J, Ahn W, Kim C . Accelerated wound healing by smad3 antisense oligonucleotides-impregnated chitosan/alginate polyelectrolyte complex. Biomaterials. 2008; 29(36):4831-7. DOI: 10.1016/j.biomaterials.2008.08.023. View

14.

Rutnam Z, Wight T, Yang B . miRNAs regulate expression and function of extracellular matrix molecules. Matrix Biol. 2012; 32(2):74-85. PMC: 4106267. DOI: 10.1016/j.matbio.2012.11.003. View

15.

Meister G, Landthaler M, Dorsett Y, Tuschl T . Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA. 2004; 10(3):544-50. PMC: 1370948. DOI: 10.1261/rna.5235104. View

16.

Yang X, Rutnam Z, Jiao C, Wei D, Xie Y, Du J . An anti-let-7 sponge decoys and decays endogenous let-7 functions. Cell Cycle. 2012; 11(16):3097-108. PMC: 3442920. DOI: 10.4161/cc.21503. View

17.

Krutzfeldt J, Rajewsky N, Braich R, Rajeev K, Tuschl T, Manoharan M . Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005; 438(7068):685-9. DOI: 10.1038/nature04303. View

18.

Speight P, Nakano H, Kelley T, Hinz B, Kapus A . Differential topical susceptibility to TGFβ in intact and injured regions of the epithelium: key role in myofibroblast transition. Mol Biol Cell. 2013; 24(21):3326-36. PMC: 3814143. DOI: 10.1091/mbc.E13-04-0220. View

19.

Yang X, Du W, Li H, Liu F, Khorshidi A, Rutnam Z . Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res. 2013; 41(21):9688-704. PMC: 3834805. DOI: 10.1093/nar/gkt680. View

20.

Roy S, Sen C . miRNA in wound inflammation and angiogenesis. Microcirculation. 2012; 19(3):224-32. PMC: 3399420. DOI: 10.1111/j.1549-8719.2011.00156.x. View