UCI researchers reveal essential role of mecha

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image: PIEZO1 accumulates at the edge of the wound to slow healing.
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Credit: UCI School of Medicine

Irvine, CA – November 9, 2021 – PIEZO1, an ion channel mechanosensor found in cells, has been shown to play a key role in regulating the rate of healing of skin wounds by researchers at the University of California at Irvine (UCI).

Posted today in eLife, the study, entitled “The spatiotemporal dynamics of PIEZO1 localization controls the migration of keratinocytes during wound healing”, Found that in mice lacking the PIEZO1 ion channel protein in keratinocytes, skin wounds heal faster than in mice with increased PIEZO1 function in keratinocytes.

“Our collaborators from Ardem Patapoutian’s laboratory at the Scripps Research Institute observed that in mice with reduced PIEZO1, healing is faster. We wanted to determine the ‘How? ‘Or’ What’, ‘when’ and ‘or’ of the implication of PIEZO1, in order to find potential treatments which could accelerate the cure ”, declared Medha Pathak, PhD, Assistant Professor in the Department of Physiology and Biophysics of the UCI Faculty of Medicine. “For this, my laboratory has developed new approaches to visualize PIEZO1 during wound healing. in vitro.

PIEZO1 is one of a number of other proteins that can sense mechanical signals and provide instructions on what actions the cell should take. Previous research has suggested that mechanosensors play a role in wound closure, but the specific mechanosensor involved was unknown. This was the first study in which the role of PIEZO1 in wound healing was investigated.

The skin, the largest organ in the body, protects against external aggressions while allowing touch. Injury to the skin interferes with these functions and puts the body at increased risk for infection, disease, and scar formation. During healing, keratinocytes, the most abundant cell type in the top layer of the skin, move inward from the wound edges to close the wound space. This helps to restore the skin barrier, restoring the protective function of the skin.

“Previous field studies have shown that mechanical signals regulate the migration of keratinocytes during wound healing. Here, we show that in keratinocytes, PIEZO1 actually acts as the mechanosensor that processes these signals to regulate the rate of wound healing. To our surprise, we found that PIEZO1 accumulates at the wound edge and inhibits healing, ”said lead author Jesse Holt, graduate student at Pathak Lab.

The results of this study provide insight into how wound healing occurs and have the potential to guide research into new wound healing treatments. However, more research needs to be done to confirm that reducing the activity of PIEZO1 does not cause unwanted effects, such as reduced tactile sensation, and human testing will be needed.

PIEZO1 has been identified as a key ion channel with various important physiological roles. Co-author of this study and winner of the 2021 Nobel Prize Ardem Patapoutian, PhD, professor of neuroscience and researcher at the Howard Hughes Medical Institute at Scripps Research, is well known for his work characterizing the ion channels PIEZO1, PIEZO2 and TRPM8. PIEZO1 is emerging as an active research area at UCI: Michael Cahalan, PhD, Chairman of the Department of Physiology and Biophysics at UCI School of Medicine, and Wendy Liu, Professor of Biomedical Engineering are also studying PIEZO1 , in the immune system. In May 2021, Liu, Cahalan and Pathak laboratories united reported on the role of protein in macrophages and the response to foreign bodies; and in July 2021, Cahalan and Pathak laboratories published a to study identifying PIEZO1 as having an important role in T cell function linked to autoimmune neuroinflammatory disorders.

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This study was funded in part by the National Institutes of Health, the Howard Hughes Medical Institute, the George Hewitt Foundation for Medical Research, the National Science Foundation, and the Simons Foundation.

About the UCI School of Medicine

Each year, the UCI School of Medicine trains more than 400 medical students, and nearly 150 doctoral and master’s students. More than 700 residents and scholarship holders are trained at the UCI medical center and affiliated institutions. The School of Medicine offers an MD; a dual MD / PhD medical scientist training program; and doctorates and masters in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students can also pursue an MD / MBA, MD / Masters in Public Health, or MD / Masters through one of three mission-oriented programs: Health Education to Advance Leaders in Integrative Medicine ( HEAL-IM), Leadership Education to Advance African, Black and Caribbean Diversity (LEAD-ABC) and the Latin American Community Medical Education Program (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks in the top 50 nationally researched. For more information visit som.uci.edu.


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