The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

Author:

Jiang Dongsheng1ORCID,Guo Ruiji12,Dai Ruoxuan1,Knoedler Samuel123ORCID,Tao Jin45,Machens Hans-Günther2,Rinkevich Yuval1

Affiliation:

1. Institute of Regenerative Biology and Medicine, Helmholtz Center Munich, 81377 Munich, Germany

2. Department of Plastic and Hand Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany

3. Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02152, USA

4. Department of Physiology and Neurobiology and Centre for Ion Channelopathy, Medical College of Soochow University, Suzhou 215123, China

5. Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou 215123, China

Abstract

The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such as mechanical stress, osmotic pressure, and temperature. TRPV4 enables the entry of cation ions, particularly calcium ions, into the cell. Activation of TRPV4 channels initiates calcium oscillations, which trigger intracellular signaling pathways involved in a plethora of cellular processes, including tissue repair. Widely expressed throughout the body, TRPV4 can be activated by a wide array of physicochemical stimuli, thus contributing to sensory and physiological functions in multiple organs. This review focuses on how TRPV4 senses environmental cues and thereby initiates and maintains calcium oscillations, critical for responses to organ injury, tissue repair, and fibrosis. We provide a summary of TRPV4-induced calcium oscillations in distinct organ systems, along with the upstream and downstream signaling pathways involved. In addition, we delineate current animal and disease models supporting TRPV4 research and shed light on potential therapeutic targets for modulating TRPV4-induced calcium oscillation to promote tissue repair while reducing tissue fibrosis.

Funder

European Research Council Consolidator

LEO Foundation

European Foundation for the Study of Diabetes (EFSD) Anniversary Fund Program

German Research Foundation

European Union Horizon 2020

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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5. The TRP superfamily of cation channels;Montell;Sci. STKE,2005

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