| First Author | Liu Z | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 9 | Pages | 10165-10176 |
| PubMed ID | 31207192 | Mgi Jnum | J:289334 |
| Mgi Id | MGI:6435012 | Doi | 10.1096/fj.201900376RRR |
| Citation | Liu Z, et al. (2019) beta-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation. FASEB J 33(9):10165-10176 |
| abstractText | Gastrointestinal toxicity limits the clinical application of abdominal and pelvic radiotherapy and currently has no effective treatment. Intestinal leucine-rich-repeat-containing GPCR 5 (Lgr5)-positive stem cell depletion and loss of proliferative ability due to radiation may be the primary factors causing intestinal injury following radiation. Here, we report the critical role of beta-arrestin1 (betaarr1) in radiation-induced intestinal injury. Intestinal betaarr1 was highly expressed in radiation enteritis and in a radiation model. betaarr1 knockout (KO) or knockdown mice exhibited increased proliferation in intestinal Lgr5+ stem cell, crypt reproduction, and survival following radiation. Unexpectedly, the beneficial effects of betaarr1 deficiency on intestinal stem cells in response to radiation were compromised when the endoplasmic reticulum stress-related protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor-2alpha (eIF2alpha) pathway was inhibited, and this result was further supported in vitro. Furthermore, we found that betaarr1 knockdown with small interfering RNA significantly enhanced intestinal Lgr5(+) stem cell proliferation after radiation via directly targeting PERK. betaarr1 offers a promising target for mitigating radiation-induced intestinal injury.-Liu, Z., Jiang, J., He, Q., Liu, Z., Yang, Z., Xu, J., Huang, Z., Wu, B. beta-Arrestin1-mediated decrease in endoplasmic reticulum stress impairs intestinal stem cell proliferation following radiation. |
