Colonic Dysmotility Regulated by Downregulation of PDGFRα+ Cells / SK3 Channel in DSS-induced Colitis Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Dec 17

PMID 39689119

Authors

Chen Lu

Hongxia Zhu

Haiqian Lu

Xianjing Xie

Ling Tong

Yujia Li

Zhida Qian

Affiliations

Soon will be listed here.

Abstract

Colitis is a complex multifactorial disease with an unknown aetiology that mainly manifests as chronic refractory colon transmission disorders. Smooth muscle, the main source of colon transmission power, consists of not only smooth muscle cells (SMCs) but also PDGFRα+ cells that mediate smooth muscle relaxation and ICCs that mediate contraction. PDGFRα+ cells and their unique small conductance Ca2+-activated K (SK3) channels are crucial in regulating colonic transit by exerting inhibitory effects. In this study, the contributions of the SK3 signalling pathway in PDGFRα+ cells to colitis-induced colonic transit dysmotility were investigated in DSS-induced colitis mice. An experiment was conducted to record the transmission of waves during smooth muscle contraction in the colon, using a colonic migrating motor complex(CMMC). Western blotting was utilized for protein expression detection, while PCR was employed for gene expression analysis. Immunofluorescence staining was used to detect the co-localization of SK3 channels with PDGFRα+ cells. In the colitis group, the weight of mice was reduced, the length of colon was shortened, and the disease activity index (DAI) was significantly increased. In the CMMC experiment, colon transmission was significantly disrupted in the colitis group compared to the control group, with a consistent colonic transmission amplitude and frequency. The sensitivity of mice with colitis to SK3 antagonists and agonists (apamin and CyPPA) was lower than that of the control group in CMMC experiment. The expression levels of mRNA and protein of PDGFRα and SK3 channels in colon of mice with colitis were decreased. Less SK3 channel colocalization with PDGFRα+ cells was observed in the colitis mouse group than in the control group. The findings indicated that colonic transit disorder in DSS-induced colitis mice is caused by the down-regulation of PDGFRα+ cells / SK3 channel expression.

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