Multi-biological functions of intermedin in diseases

Zhi Yang; Hongchun Li; Pengfei Wu; Qingyan Li; ChunYan Yu; Denian Wang; Weimin Li

doi:10.3389/fphys.2023.1233073

Multi-biological functions of intermedin in diseases

Front Physiol. 2023 Sep 6:14:1233073. doi: 10.3389/fphys.2023.1233073. eCollection 2023.

Authors

Zhi Yang^#^{1

2}, Hongchun Li^#³, Pengfei Wu⁴, Qingyan Li¹, ChunYan Yu⁵, Denian Wang^{1

4}, Weimin Li^{1

4}

Affiliations

¹ Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
³ National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
⁴ Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁵ Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

Intermedin (IMD) is a member of the calcitonin gene-related peptide (CGRP)/calcitonin (CT) superfamily, and it is expressed extensively throughout the body. The typical receptors for IMD are complexes composed of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP), which leads to a biased activation towards Gα_s. As a diagnostic and prognostic biomarker, IMD regulates the initiation and metastasis of multiple tumors. Additionally, IMD functions as a proangiogenic factor that can restrain excessive vascular budding and facilitate the expansion of blood vessel lumen, ultimately resulting in the fusion of blood vessels. IMD has protective roles in various diseases, including ischemia-reperfusion injury, metabolic disease, cardiovascular diseases and inflammatory diseases. This review systematically elucidates IMD's expression, structure, related receptors and signal pathway, as well as its comprehensive functions in the context of acute kidney injury, obesity, diabetes, heart failure and sepsis. However, the precise formation process of IMD short peptides in vivo and their downstream signaling pathway have not been fully elucidated yet. Further in-depth studies are need to translate IMD research into clinical applications.

Keywords: Intermedin (IMD); calcitonin gene-related peptide (CGRP); cardiovascular diseases; metabolic syndrome; sepsis; tumor.

Publication types

Review

Grants and funding

The National Natural Science Foundation of P.R. China (82102301). The Natural Science Foundation of Sichuan Province (2021YJ0418). Figures in the article were created with BioRender.com.