The roles of PDGFRα signaling in the postnatal development and functional maintenance of the SMC-ICC-PDGFRα+ cell (SIP) syncytium in the colon.

Autor: Lin Q; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Qin M; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Zhao SG; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Liu ZX; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Dou WJ; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Zhang R; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Li YL; Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, China., Xi XH; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Xu JQ; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Ma LT; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China., Wang JJ; Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2019 May; Vol. 31 (5), pp. e13568. Date of Electronic Publication: 2019 Mar 07.
DOI: 10.1111/nmo.13568
Abstrakt: 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.
(© 2019 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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