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The roles of PDGFRα signaling in the postnatal development and functional maintenance of the SMC‐ICC‐PDGFRα+ cell (SIP) syncytium in the colon
Author(s) -
Lin Qiang,
Qin Ming,
Zhao Shuguang,
Liu Zhenxiong,
Dou Weijia,
Zhang Rong,
Li Yulong,
Xi Xiaohou,
Xu Jiaqiao,
Ma Litian,
Wang Jingjie
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13568
Subject(s) - interstitial cell of cajal , platelet derived growth factor receptor , syncytium , caldesmon , myenteric plexus , pathology , biology , microbiology and biotechnology , receptor , cancer research , medicine , cell , growth factor , immunohistochemistry , genetics , calmodulin , calcium
Background 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. Methods 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. Key Results A dose of 5 mg(kg•day) −1 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) −1 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) −1 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.