RIPK1 and RIPK3 inhibitors: potential weapons against inflammation to treat diabetic complications

Dan Ke; Zhen Zhang; Jieting Liu; Peijian Chen; Yucen Dai; Xinhai Sun; Yanhui Chu; Luxin Li

doi:10.3389/fimmu.2023.1274654

RIPK1 and RIPK3 inhibitors: potential weapons against inflammation to treat diabetic complications

Front Immunol. 2023 Oct 26:14:1274654. doi: 10.3389/fimmu.2023.1274654. eCollection 2023.

Authors

Dan Ke^#^{1

2}, Zhen Zhang^#^{2

3}, Jieting Liu^#^{1

2}, Peijian Chen^{1

2}, Yucen Dai^{1

2}, Xinhai Sun⁴, Yanhui Chu², Luxin Li^{1

2}

Affiliations

¹ College of Life Sciences, Mudanjiang Medical University, Mudanjiang, China.
² Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Mudanjiang, China.
³ School of First Clinical Medical College, Mudanjiang Medical University, Mudanjiang, China.
⁴ Department of Thoracic Surgery, Union Hospital, Fujian Medical University, Fuzhou, China.

^# Contributed equally.

Abstract

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia due to a variety of etiological factors. Long-term metabolic stress induces harmful inflammation leading to chronic complications, mainly diabetic ophthalmopathy, diabetic cardiovascular complications and diabetic nephropathy. With diabetes complications being one of the leading causes of disability and death, the use of anti-inflammatories in combination therapy for diabetes is increasing. There has been increasing interest in targeting significant regulators of the inflammatory pathway, notably receptor-interacting serine/threonine-kinase-1 (RIPK1) and receptor-interacting serine/threonine-kinase-3 (RIPK3), as drug targets for managing inflammation in treating diabetes complications. In this review, we aim to provide an up-to-date summary of current research on the mechanism of action and drug development of RIPK1 and RIPK3, which are pivotal in chronic inflammation and immunity, in relation to diabetic complications which may be benefit for explicating the potential of selective RIPK1 and RIPK3 inhibitors as anti-inflammatory therapeutic agents for diabetic complications.

Keywords: diabetes; diabetic complications; inflammation; receptor interacting protein kinase; regulatory cell death.

Publication types

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

MeSH terms

Diabetes Complications* / drug therapy
Diabetes Mellitus* / drug therapy
Diabetes Mellitus* / etiology
Diabetic Nephropathies*
Humans
Inflammation / drug therapy
Inflammation / metabolism
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
Serine
Threonine

Substances

Receptor-Interacting Protein Serine-Threonine Kinases
Threonine
Serine
RIPK1 protein, human
RIPK3 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Local Colleges and Universities Talent Development Funding from Heilongjiang Provincial Department of Finance (No. 2020GSP09), the Natural Science Foundation of Heilongjiang Province (No. LH2022H099), the Basic Scientific Research Project of University belongs to Heilongjiang (No. 2021-KYYWF-0519), the Heilongjiang Provincial Key Research and Development Program (No. GZ20210121), the Torch Program of Mudanjiang Medical University (No. 2022-MYHJ-003) and the Project of Young Innovative Talents Training Program of Regular Undergraduate Colleges and Universities in Heilongjiang Province (No. UNPYSCT-2020064).