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[Nuclear factor-κB pathway mediates the effects of CD137 signaling on NFATc1 expression in mice vascular smooth

Yunjie Yin1, Jinchuan Yan2, Zhongqun Wang1

  • 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

Zhonghua Xin Xue Guan Bing Za Zhi
|October 1, 2015
PubMed
Abstract

Insights

CD137 signaling activates the nuclear factor-kappaB (NF-κB) pathway, leading to increased nuclear factor of activated T cells c1 (NFATc1) expression in mouse aortic vascular smooth muscle cells (VSMCs). This pathway is crucial for regulating NFATc1 in VSMCs.

Area of Science:

  • Immunology
  • Cell Biology
  • Vascular Biology

Background:

  • Vascular smooth muscle cells (VSMCs) play a critical role in vascular homeostasis and disease.
  • CD137 is a co-stimulatory molecule known for its role in immune responses.
  • The involvement of CD137 signaling in VSMCs and its downstream pathways remains incompletely understood.

Purpose of the Study:

  • To investigate the effect of CD137 signaling on nuclear factor of activated T cells c1 (NFATc1) expression in mouse aortic VSMCs.
  • To elucidate the role of the nuclear factor-kappaB (NF-κB) pathway in mediating CD137-induced NFATc1 regulation.

Main Methods:

  • Primary culture of mouse aortic VSMCs using tissue explant adherence methods.
  • Detection of mRNA expression for CD137 and NFATc1 via real-time quantitative PCR (RT-qPCR).
  • Assessment of protein expression (IκB-α, NF-κB p65, phospho-p65, NFATc1) using Western blot and CD137 levels by Flow Cytometry (FCM).

Main Results:

  • CD137 expression was significantly upregulated in VSMCs upon TNF-α co-culture.
  • CD137 signaling activated the NF-κB pathway, evidenced by increased phospho-p65 and decreased IκB-α, an effect reversible by an NF-κB inhibitor (PDTC).
  • NFATc1 mRNA and protein expression were significantly upregulated by CD137 signaling, with effects reversed by PDTC.

Conclusions:

  • CD137 signaling modulates NFATc1 expression in VSMCs.
  • The NF-κB pathway is a key mediator of CD137-induced NFATc1 regulation in VSMCs.
  • These findings highlight a novel role for CD137 signaling in vascular smooth muscle cells.

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