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
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 (LS...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/21/2524 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nagendra Verma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T11:32:36Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T11:32:36Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-61b6eed21c8d47d7828e224dd6876eec2023-11-10T15:00:38ZengMDPI AGCells2073-44092023-10-011221252410.3390/cells12212524MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic CorneasNagendra Verma0Drirh Khare1Adam J. Poe2Cynthia Amador3Sean Ghiam4Andrew Fealy5Shaghaiegh Ebrahimi6Odelia Shadrokh7Xue-Ying Song8Chintda Santiskulvong9Mitra Mastali10Sarah Parker11Aleksandr Stotland12Jennifer E. Van Eyk13Alexander V. Ljubimov14Mehrnoosh Saghizadeh15Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAGenomics Core, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAGenomics Core, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USAEpithelial 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.https://www.mdpi.com/2073-4409/12/21/2524diabetic corneaextracellular vesiclesexosomecellular crosstalkmiRNAlimbal stem cells |
| spellingShingle | 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 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 Cells diabetic cornea extracellular vesicles exosome cellular crosstalk miRNA limbal stem cells |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | diabetic cornea extracellular vesicles exosome cellular crosstalk miRNA limbal stem cells |
| url | https://www.mdpi.com/2073-4409/12/21/2524 |
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