Hebert Sadie L, Fitzpatrick Krysta R, McConnell Samantha A, Cucak Anja, Yuan Ching, McLoon Linda K
Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, United States.
Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, United States; Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States.
Exp Cell Res. 2017 Dec 1;361(1):101-111. doi: 10.1016/j.yexcr.2017.10.007. Epub 2017 Oct 7.
One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7. EOM-derived and LEG-derived EECD34 cells were treated with vehicle, retinoic acid, the RXR agonist bexarotene, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG-derived cells expressed desmin and fused when treated with retinoic acid compared to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We hypothesize that retinoic acid signaling aids in the maintenance of large numbers of undifferentiated myogenic precursor cells in the EOM, which would be required to maintain EOM normalcy throughout a lifetime of myonuclear turnover.
肢体肌肉和眼外肌（EOM）之间的一个主要区别在于，与肢体肌肉相比，眼外肌中存在大量富含Pitx2的生肌前体细胞。我们假设视黄酸调节眼外肌生肌前体细胞中Pitx2的表达，并且其作用在腿部肌肉中会有所不同。这两组肌肉表达不同水平的视黄酸受体（RAR）和类视黄醇X受体（RXR）。RXR与Pitx2阳性细胞共定位，但不与表达Pax7的细胞共定位。用载体、视黄酸、RXR激动剂贝沙罗汀、RAR反向激动剂BMS493或RXR拮抗剂UVI 3003处理源自眼外肌和腿部的EE CD34细胞。在体外，与载体处理相比，用视黄酸处理时，源自眼外肌的EE CD34细胞中表达结蛋白并融合的细胞较少，而源自腿部的细胞中表达结蛋白并融合的细胞较多。与载体处理相比，暴露于视黄酸的源自眼外肌和腿部的EE CD34细胞中表达Pitx2的细胞百分比更高，这支持了视黄酸在维持Pitx2表达中起作用的假设。我们假设视黄酸信号传导有助于维持眼外肌中大量未分化的生肌前体细胞，这是在整个肌核更新生命周期中维持眼外肌正常状态所必需的。
