The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Fang Zhao; Yini He; Zhihao Zhao; Jiarong He; Hong Huang; Kelong Ai; Liang Liu; Xiong Cai

doi:10.3389/fimmu.2023.1272133

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Front Immunol. 2023 Oct 26:14:1272133. doi: 10.3389/fimmu.2023.1272133. eCollection 2023.

Authors

Fang Zhao^{1

2}, Yini He¹, Zhihao Zhao³, Jiarong He⁴, Hong Huang¹, Kelong Ai², Liang Liu⁵, Xiong Cai¹

Affiliations

¹ Department of Rheumatology of The First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
² Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.
³ Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
⁴ Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ State Key Laboratory of Dampness Syndrome of Chinese Medicine, The 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Abstract

Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA's angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.

Keywords: Notch signaling; adipokines; angiogenesis; epigenetic regulation; rheumatoid arthritis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / pathology
Epigenesis, Genetic*
Humans
Inflammation / pathology
Neovascularization, Pathologic / pathology
Synovial Membrane / pathology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by grants from the National Natural Science Foundation of China General Program (82274506), Science and Technology Innovation Program of Hunan Province (2020SK1020, 2021RC4035), Open-Competing Disciple Construction Project of Hunan University of Chinese Medicine (HNUCM) (22JBZ003), Hunan Furong Distinguished Scholar Program (XJT[2020]58), Hunan 121 Training Project for Innovative Talents (XRSH[2019]192), the Chinese Academy of Engineering Academician Liang Liu’s Workstation Project of HNUCM (KH[2021]4-21YS001) and World First-class Discipline Incubation Project of HNUCM (XJF[2022]57).