Kininogen-Nitric Oxide Signaling at Nearby Nonexcited Acupoints after Long-Term Stimulation

Ting Wang; Geng Zhu; Liyue Qin; Qian Wang; Chen She; Dongsheng Xu; Weiwei Hu; Kenghuo Luo; Ying Lei; Yanling Gong; Arijit Ghosh; Dongni Ma; Chun-Lei Ding; Bu-Yi Wang; Yang Guo; Shou-Shan Ma; Michihiro Hattori; Yutaka Takagi; Katsutoshi Ara; Kazuhiko Higuchi; Xingwang Li; Lin He; Wanzhu Bai; Koichi Ishida; Sheng-Tian Li

doi:10.1016/j.xjidi.2021.100038

Kininogen-Nitric Oxide Signaling at Nearby Nonexcited Acupoints after Long-Term Stimulation

JID Innov. 2021 Jun 24;1(3):100038. doi: 10.1016/j.xjidi.2021.100038. eCollection 2021 Sep.

Authors

Ting Wang^{1

2

3}, Geng Zhu^{1

4}, Liyue Qin^{1

3}, Qian Wang¹, Chen She³, Dongsheng Xu⁵, Weiwei Hu¹, Kenghuo Luo¹, Ying Lei³, Yanling Gong¹, Arijit Ghosh¹, Dongni Ma¹, Chun-Lei Ding¹, Bu-Yi Wang¹, Yang Guo¹, Shou-Shan Ma¹, Michihiro Hattori³, Yutaka Takagi³, Katsutoshi Ara³, Kazuhiko Higuchi³, Xingwang Li¹, Lin He¹, Wanzhu Bai⁵, Koichi Ishida³, Sheng-Tian Li^{1

2

6}

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
² Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
³ Kao China Research and Development Center, Shanghai, China.
⁴ Department of Biomedical Engineering, School of Medical Instrument, Shanghai University of Medicine & Health Sciences, Shanghai, China.
⁵ Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
⁶ Shanghai Key Laboratory of Psychotic Disorders, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. We found that kininogen expression was significantly upregulated in the stimulated and the nonstimulated adjacent acupoints along the same meridian. The enhanced kininogen expression was meridian dependent and was most apparent among small vessels in the subcutaneous layer. Enhanced signals of nitric oxide synthases, cGMP-dependent protein kinase, and myosin light chain were also observed at the nonstimulated adjacent acupoints along the same meridian. These findings uncover biological changes at acupoints and suggest the critical role of the kininogen-nitric oxide signaling pathway in acupoint activation.

Keywords: CEP, catgut embedding; KNG, kininogen; MLC, myosin light chain; NO, nitric oxide; NOS, nitric oxide synthase; PKG, protein kinase G; iTRAQ, isobaric tags for relative and absolute quantitation; sCEP, sham catgut embedding.