Exosomal miR-214 from endometrial stromal cells inhibits endometriosis fibrosis.


Exosomal miR-214 from endometrial stromal cells inhibits endometriosis fibrosis.

Is it possible to prevent fibrosis in endometriosis by microRNA-214 delivery in exosomes?

Key Points

Highlight:

  • Upregulation of miR-214 may inhibit fibrogenesis and its delivery by exosomes derived from ectopic endometrial stromal cells (ESCs), offers an alternative therapeutic approach for endometriosis fibrosis.

What’s known already:

  • miR-214 plays an important role in fibrotic disease.     
  • Connective tissue growth factor (CTGF) is a critical fibrogenic mediator of miR-214.
  • The expression of miR-214 is decreased in ectopic ESCs compared with normal ESCs.
  • miRNAs are a natural cargo of exosomes and these could be exploited as carriers of miRNA in replacement therapy.

What’s done here:

  • CTGF and fibrotic markers upregulation in endometriosis are associated with a reciprocal down-regulation of miR-214.
  • By using miR-214 mimics and antagonists to investigate the expression of fibrotic markers, Dr. Miao group from China found that increased production of miR-214 reduced Collagen-αI and CTGF expression in endometriosis stromal and endometrial epithelial cells in response to fibrosis-inducing stimuli.
  • Ectopic ESCs yielded nano-sized exosomes which expressed miR-214.
  • Loading exosomes with miR-214 mimic and injecting them into an experimental endometriosis mouse model resulted in a decrease in the expression of fibrosis-associated proteins.

Limitation and Implication:

  • This group only isolated exosomes from ectopic ESCs, whether this is the optimum source requires further study.
  • Upregulation of miRNA-214 potentially offers an alternative therapeutic approach for endometriosis fibrosis.

Lay Summary

Fibrosis is an important pathological feature of endometriosis. Novel therapies targeting the mechanisms of fibrosis in endometriosis are indispensable for the development of strategies to prevent and treat endometriosis.

Previous microarray studies have detected some miRNAs that are aberrantly expressed in endometriosis. miR-214, one of the miRNAs down-regulated in human endometriotic cyst stromal cells (ECSCs), is known to have fibrosis-suppressor roles, including the inhibition of fibroblast proliferation, collagen synthesis, and the epithelial-mesenchymal transition process. However, it remains unclear whether the miR-214 involved in the pathogenesis of endometriosis fibrosis targets connective tissue growth factor (CTGF), which is a predicted target molecule of miR-214.

Here, Dr. Miao group from Capital Medical University at China test the hypothesis that miR-214 expression is reduced in fibrotic endometriosis and aberrant epigenetic regulation of CTGF may mediate the mechanisms of fibrogenesis in endometriosis. In this study, Dr. Miao aimed to evaluate whether exosomes loaded with miR-214 could reverse fibrosis by targeting CTGF in a xenograft model of endometriosis using immunodeficient nude mice.

CTGF and fibrotic markers upregulation in endometriosis are associated with a reciprocal down-regulation of miR-214. By using miR-214 mimics and antagomirs to investigate the expression of fibrotic markers, this group found that increased production of miR-214 reduced Collagen αI and CTGF expression in endometriosis stromal and endometrial epithelial cells in response to fibrosis-inducing stimuli. Loading exosomes with miR-214 mimic and injecting them into an experimental endometriosis mouse model resulted in a decrease in the expression of fibrosis-associated proteins.

One major limitation is that this group isolated exosomes from ectopic ESCs, whether this is the optimum source requires further study. Dr. Miao group believe that upregulation of miRNA-214 potentially offers an alternative therapeutic approach for endometriosis fibrosis.


Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29660008


endometriosis fibrosis miR-214 CTGF exosome

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