Piezo1 identified as a key release of the extension of the powered skin with voltage

Researchers from Johns Hopkins Medicine report new evidence that PIEZO1 protein controls skin growth by detection when the skin is stretched, and then coordinating metabolic and immunological changes necessary for growth. Experts say that discoveries can ultimately help doctors develop non -invasive therapeutic approaches in order to create new skin to treat burns and other injuries requiring skin transplantation.

Scientists have long understood that too much physical stress, defined as internal and external tension experienced by cells and structures in the body, causes the skin to break, but moderate levels promote growth, such as body changes observed during the development of the child and pregnancy.

The increase in the skin based on the tension includes the epidermis (the most outer layer of the skin) and the skin of the skin (medium skin layer), but the way in which the molecular is controlled was unclear. In contrast, researchers know that wound healing, a different process including skin growth, is controlled by the hippo signal trail and requires coordination between blood, fat, immunity, nerves and skin.

Earlier studies have shown that PIEZO1, the so -called Mechanotransducer protein, which turns physical strength into practical biological signals, was present at a high level of skin, which suggests a potential role in skin development.

In the set of experiments financed by NIH published on July 25, the research team led by JHM decided to examine how Piezo1 can sense and react to mechanical stretching first, identifying molecular signals caused when the skin is stretched in the mouse, and then examining how these signals can contribute to growth when Piezo1 is manipulated.

According to Dr. Yingchao Xue, the first author of the research and research of a collaborator at the Garza laboratory at Johns Hopkins University School of Medicine, the team used the analytical method known as spatial transcriptom to compare the levels of gene expression and physical locations of where genes were activated between samples of skin collected 14, 32 and 70 days.

In extended samples, the team stated that the results of the Angiogenesis gene signature and stress granulation created on the basis of existing literature increased by 2.1 times, 1.4 times and 1.4 times, respectively. Increased results and increased immune cell activity occur in samples indicated a systemic, coordinated response to increased skin tone.

“Existing literature has shown that the paths we identified were strictly correlated with Piezo1 expression,” says Xue. One of the routes, the TGF-Beta signal trail, regulates the function of the immune system and cell growth.

Delving to examine the role of PIEZO1, the team tried to discover how the growing or decreasing activity of PIEZO1 would change skin growth based on suspense.

To do this, investigators treated the group of mice for the first time with the activator Piezo1, Yoda1. Have noticed that Yoda1 treatment increased the expression associated with tension inflammation and metabolism routes in a shorter time than initially observed in extended mice compared to indefinite mice, causing a 130% increase in skin surface, 120% increase in skin weight and 130% increase in epidermal thickness compared to non -treated control mice.

Since the increase in PIZO1 expression, the trail expression has been additionally reinforced, we were able to show that this is a key skin growth trigger. “

Dr Yingchao XUE, first author of the community research and research in Garza Laboratory at Johns Hopkins University School of Medicine

Then the group created the “Nokaut” Piezo1 mouse line, in which the PIEZO1 protein was selectively removed from the skin after tamoxifen treatment. In an average of 0.9, a knockout of a 0.9 -fold skin surface, 0.84 times a decrease in skin weight and 0.80 times the skin thickness was observed compared to control, which shows that the absence of Piezo1 negatively affects the body’s ability to adapt and grow.

Together, Xue says, it is believed that discoveries are the first to show that PIEZO1 plays a key role in regulating molecular lesions necessary for the skin’s abilities to grow in response to mechanical stress.

Researchers say that the examination can develop the search for safe and effective ways of growing skin, which would help patients undergoing reconstructive operation of burns, injuries or congenital defects. Current methods, such as silicone expanders, are time consuming and can cause complications, including skin infections.

In the future, the research team plans to examine how their discoveries translate into people.

The study was supported by the National Institute of Arthritis and Musculoszeklet and skin diseases (R01ar074846, R56AR082660), National Institute on Agging (P30Ag021334), Research Fund Daniel Nathans, Maryland Stem Stem Cell Research Fund (2022-MSCRFD-5917) and Daniel) Research prize.

Luis A. Garza, Dr. MD, received support for subsidies and payment of license fees from Sun Pharma Advanced Research Company (Sparc) under a license agreement with a group that is not related to the study. Other authors report a lack of interest conflicts.

Other researchers Johns Hopkins involved in the study are Elizabeth Winnicki, Zhaoxu Zhang, Ines Lopez, Saifeng Wang, Charles Kirby, Sam Lee, Ang Li, Chawon Lee, Hana Minsky, Kaitlin Williams, Kevin Yueh-Hsun Yang, Sashank K. Reddy and Luis A. Garz.