| First Author | Park JW | Year | 2019 |
| Journal | Stem Cells | Volume | 37 |
| Issue | 9 | Pages | 1212-1222 |
| PubMed ID | 31102490 | Mgi Jnum | J:291318 |
| Mgi Id | MGI:6446481 | Doi | 10.1002/stem.3036 |
| Citation | Park JW, et al. (2019) Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory Response. Stem Cells 37(9):1212-1222 |
| abstractText | The mammalian target of rapamycin (mTOR) signaling is critical to the regulation of stem cell maintenance and function in a cell-type and context-dependent manner. However, the effects of mTOR signaling on corneal epithelial stem cells (CESCs) under inflammatory conditions are not clear. Here, we demonstrate that mTOR inhibition with rapamycin promotes apoptosis of CESCs in a mouse model of sterile inflammation-induced CESC deficiency, and thereby aggravates the disease. Apoptosis induction in CESCs by rapamycin is not due to direct effect of rapamycin on the cells, but mediated by increase in neutrophilic inflammation. The interleukin (IL)-10/signal transducer and activator of transcription 3 anti-inflammatory pathway was downregulated in a Toll-like receptor 2-independent manner after rapamycin treatment and IL-10 replenishment abrogated the effects of rapamycin on inflammation and CESC apoptosis. Hence, our data reveal that the mTOR signaling is implicated in the control of the pro-inflammatory and anti-inflammatory balance in the cornea and that mTOR inhibition with rapamycin is detrimental to CESCs by accelerating inflammation-induced collateral damage to the cells. Stem Cells 2019;37:1212-1222. |
