Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, China.
Neurogastroenterol Motil. 2019 May;31(5):e13568. doi: 10.1111/nmo.13568. Epub 2019 Mar 7.
The SIP syncytium in the gut consists of smooth muscle cells, interstitial cells of Cajal, and PDGFRα+ cells. We studied the fate of SIP cells after blocking PDGFRα receptor to explore the roles of PDGFRα signaling in the postnatal development and functional maintenance of the SIP syncytium.
Crenolanib was administered to mice from P0, P10, or P50. The morphological changes in SIP cells were examined by immunofluorescence. Protein expression in SIP cells was detected by Western blotting. Moreover, colonic transit was analyzed by testing the colonic bead expulsion time.
A dose of 5 mg(kg•day) crenolanib administered for 10 days beginning on P0 apparently hindered the development of PDGFRα+ cells in the colonic longitudinal muscularis and myenteric plexus without influencing their proliferative activity and apoptosis, but this result was not seen in the colonic circular muscularis. SMCs were also inhibited by crenolanib. A dose of 7.5 mg(kg•day) crenolanib administered for 15 days beginning on P0 caused reductions in both PDGFRα+ cells and ICC in the longitudinal muscularis, myenteric plexus, and circular muscularis. However, when crenolanib was administered at a dose of 5 mg(kg•day) beginning on P10 or P50, it only noticeably decreased the number of PDGFRα+ cells in the colonic longitudinal muscularis. Crenolanib also caused PDGFRα+ cells to transdifferentiate into SMC in adult mice. Colonic transit was delayed after administration of crenolanib.
CONCLUSIONS & INFERENCES: Therefore, PDGFRα signaling is essential for the development and functional maintenance of the SIP cells, especially PDGFRα+ cells.
肠道中的 SIP 合胞体由平滑肌细胞、Cajal 间质细胞和 PDGFRα+细胞组成。我们研究了阻断 PDGFRα 受体后 SIP 细胞的命运，以探索 PDGFRα 信号在 SIP 合胞体的出生后发育和功能维持中的作用。
从 P0、P10 或 P50 开始，给小鼠施用 crenolanib。通过免疫荧光检查 SIP 细胞的形态变化。通过 Western blot 检测 SIP 细胞中的蛋白表达。此外，通过测试结肠珠排出时间来分析结肠转运。
从 P0 开始，每天给予 5mg(kg•day)剂量的 crenolanib 持续 10 天，明显阻碍了结肠纵肌和肌间神经丛中 PDGFRα+细胞的发育，而不影响其增殖活性和细胞凋亡，但在结肠环肌中未观察到这种结果。SMC 也被 crenolanib 抑制。从 P0 开始，每天给予 7.5mg(kg•day)剂量的 crenolanib 持续 15 天，导致纵肌、肌间神经丛和环肌中的 PDGFRα+细胞和 ICC 减少。然而，当从 P10 或 P50 开始每天给予 5mg(kg•day)剂量的 crenolanib 时，它仅明显减少了结肠纵肌中的 PDGFRα+细胞数量。crenolanib 还导致 PDGFRα+细胞在成年小鼠中转分化为 SMC。给予 crenolanib 后，结肠转运延迟。
因此，PDGFRα 信号对于 SIP 细胞的发育和功能维持是必不可少的，特别是 PDGFRα+细胞。
