MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic Corneas

Nagendra Verma, Drirh Khare, Adam J. Poe, Cynthia Amador, Sean Ghiam, Andrew Fealy, Shaghaiegh Ebrahimi, Odelia Shadrokh, Xue Ying Song, Chintda Santiskulvong, Mitra Mastali, Sarah Parker, Aleksandr Stotland, Jennifer E. Van Eyk, Alexander V. Ljubimov, Mehrnoosh Saghizadeh

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Epithelial and stromal/mesenchymal limbal stem cells contribute to corneal homeostasis and cell renewal. Extracellular vesicles (EVs), including exosomes (Exos), can be paracrine mediators of intercellular communication. Previously, we described cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos in non-diabetic (N) and diabetic (DM) limbal epithelial cells (LECs). Presently, we quantify the miRNA and proteome profiles of human LEC-derived Exos and their regulatory roles in N- and DM-LSC. We revealed some miRNA and protein differences in DM vs. N-LEC-derived Exos’ cargos, including proteins involved in Exo biogenesis and packaging that may affect Exo production and ultimately cellular crosstalk and corneal function. Treatment by N-Exos, but not by DM-Exos, enhanced wound healing in cultured N-LSCs and increased proliferation rates in N and DM LSCs vs. corresponding untreated (control) cells. N-Exos-treated LSCs reduced the keratocyte markers ALDH3A1 and lumican and increased the MSC markers CD73, CD90, and CD105 vs. control LSCs. These being opposite to the changes quantified in wounded LSCs. Overall, N-LEC Exos have a more pronounced effect on LSC wound healing, proliferation, and stem cell marker expression than DM-LEC Exos. This suggests that regulatory miRNA and protein cargo differences in DM- vs. N-LEC-derived Exos could contribute to the disease state.

Original languageEnglish (US)
Article number2524
JournalCells
Volume12
Issue number21
DOIs
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • RNA-seq
  • cellular crosstalk
  • diabetic cornea
  • exosome
  • extracellular vesicles
  • limbal epithelial cells
  • limbal stem cells
  • mesenchymal stem cells
  • miRNA
  • proteomics

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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