Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 8: 939 - 948

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.08.001

Basic research

Regulatory effect of FGF2 on the expression of R-spondin 1 in mouse intestinal stromal cells

  • LI Jingcong ,
  • ZHAO Han ,
  • LIN Qiaowen ,
  • SUN Hongxiang ,
  • SU Bing ,
  • WU Ningbo
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  • 1.Department of Immunology and Microbiology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
    2.Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    3.Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
SU bing，E-mail：bingsu@sjtu.edu.cn
WU Ningbo，E-mail：wuningbo@shsmu.edu.cn.

Received date: 2025-01-03

  Accepted date: 2025-03-07

  Online published: 2025-08-28

Supported by

National Natural Science Foundation of China(32170895);Project of Science and Technology Commission of Shanghai Municipality(22ZR1480700)

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Abstract

Objective ·To preliminarily investigate the regulatory effect and underlying mechanism of fibroblast growth factor 2 (FGF2) on R-spondin 1 (Rspo1) expression in CD34+CD81+ stromal cells from the mouse colon. Methods ·Colonic CD45-CD326-CD31-GP38+CD81+Rspo1-tdTomato+ stromal cells were sorted from Rspo1-tdTomato reporter mice by flow cytometry and subsequently cultured in vitro. The expression of surface protein markers was evaluated by flow cytometry after 14 d of culture. qPCR was employed to quantify Rspo1 expression in response to stimulation with FGF2, FGF9, epidermal growth factor (EGF), platelet-derived growth factor-bb (PDGF-bb), insulin-like growth factor 1 (IGF1), or hepatocyte growth factor (HGF). RNA sequencing and bioinformatic analyses were used to identify the signaling pathways underlying FGF2-mediated regulation of Rspo1, followed by preliminary validation with pathway-specific inhibitors and qPCR. Results ·After 14 d of culture, the sorted colonic stromal cells retained expression of CD34, CD81, and glycoprotein GP38, while remaining negative for other lineages markers CD45, CD326, and CD31. qPCR revealed that 20 ng/mL FGF2 significantly suppressed Rspo1 expression, whereas the other tested growth factors exerted no notable effect. RNA sequencing and bioinformatic analysis indicated that mitogen-activated protein kinase (MAPK) signaling pathway played a key role in the regulatory effect of FGF2 on Rspo1. qPCR further demonstrated that pretreatment with U0126, an inhibitor of mitogen extracellular kinase 1/2 (MEK1/2), reversed FGF2-mediated suppression of Rspo1 expression. Conclusion ·FGF2 may inhibit Rspo1 expression in mouse colonic CD34+CD81+ stromal cells via the MEK1/2-extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway.

Key words： R-spondin 1 gene; fibroblast growth factor 2 (FGF2); CD34+CD81+ stromal cell; mitogen-activated protein kinase (MAPK) pathway

Cite this article

LI Jingcong , ZHAO Han , LIN Qiaowen , SUN Hongxiang , SU Bing , WU Ningbo . Regulatory effect of FGF2 on the expression of R-spondin 1 in mouse intestinal stromal cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(8) : 939 -948 . DOI: 10.3969/j.issn.1674-8115.2025.08.001

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