This schematic diagram exhibits how a particular inhabitants of fibroblast expressing PIEZO2 protein contribute to the formation and progress of keloids. Credit score: Professor Yuzuru Ikehara from Chiba College, Japan Picture supply: https://doi.org/10.1002/path.6455
Keloids are raised, overgrown scars that may develop after pores and skin accidents or surgical procedure, usually extending past the unique wound boundaries. For many individuals, keloids are greater than only a beauty concern; they usually trigger distressing signs equivalent to persistent ache, itching, and restricted motion. Whereas varied remedy choices exist, equivalent to surgical elimination, steroid injections, and radiation, keloids are notoriously tough to handle, with recurrence charges reaching as excessive as 30%.
Even after a long time of examine, it’s nonetheless unclear why keloids develop uncontrollably, in contrast to hypertrophic scars. The present understanding is that an overproduction of extracellular matrix collagen by fibroblasts—cells that produce parts of connective tissue—is concerned and that repeated mechanical stress on the pores and skin contributes to keloid formation. Nevertheless, the exact mobile and molecular mechanisms driving this uncontrolled scarring are unclear. Extra particularly, we do not understand how or which cells sense the mechanical strain and in the end translate it into irregular tissue progress.
Now, a examine was revealed within the The Journal of Pathology on September 1, 2025, offers a brand new piece to this puzzle. A analysis group led by Professor Yuzuru Ikehara, together with co-first authors Dr. Shinsuke Akita and Dr. Sanae Ikehara, and co-authors Prof. Kiyoshi Hirahara, and Prof. Nobuyuki Mitsukawa, all from the Graduate College of Drugs at Chiba College, Japan, investigated the histological, genetic, and molecular variations between keloids and different fibrotic circumstances to pinpoint the distinctive drivers of keloid formation and recurrence.
“While analyzing fibrotic tissue from lymphedema in collaboration with plastic surgeons, I conceived the idea that comparing it with keloid tissue might help identify pathological alterations specific to keloid fibroblasts. Although both conditions involve fibrosis, their underlying physiological contexts and etiologies differ substantially,” explains Prof. Ikehara, describing the motivation behind the examine.
The examine concerned a complete evaluation of human tissue samples. The group in contrast keloid tissues with these from lymphedema, a situation characterised by fibrous overgrowth however not primarily pushed by mechanical stress, together with wholesome pores and skin samples. They employed a number of superior strategies, together with international gene expression evaluation and single-cell RNA sequencing; these strategies allowed them to look at gene exercise in particular person cells and exactly characterize the cell varieties concerned. By way of this detailed method, the researchers sought to pinpoint mechanosensitive cells and molecules contributing to keloid pathology and recurrence.
A key discovery was that keloid tissues exhibited considerably increased expression ranges of a mechanosensitive ion channel known as PIEZO2, in comparison with lymphedema tissues. Merely put, PIEZO2 acts as a microscopic sensor, permitting cells to detect and reply to mechanical forces. The researchers noticed that keloids with a historical past of recurrence after surgical procedure confirmed even increased ranges of PIEZO2.
Additional investigation utilizing single-cell evaluation recognized a beforehand unknown subpopulation of fibroblasts that particularly expressed excessive ranges of PIEZO2. These PIEZO2-expressing fibroblasts (known as FBPZ2+) have been discovered to be extremely lively within the manufacturing of collagen and different parts of the extracellular matrix, that are the constructing blocks of scar tissue. The group additionally noticed that these FBPZ2+ cells clustered round blood and lymphatic vessels in keloid tissue, significantly in actively rising areas.
“Connective tissue is not composed merely of fibroblasts—it also contains immune cells, blood vessels, and nerves, all of which work together to maintain the proper homeostasis, a critical factor in supporting organ-specific functions,” explains Prof. Ikehara.
“Therefore, just as studies of immune and neural cell components have advanced our understanding of neurodegenerative and allergic diseases, investigating fibroblasts may help uncover the mechanisms underlying keloid formation.” Certainly, this examine represents a big step in that course by highlighting the distinctive function of FBPZ2+cells.
Most significantly, the identification of those PIEZO2-expressing fibroblasts has profound implications for the longer term analysis and remedy of keloids. The examine findings reveal that keloid formation is just not merely a generalized overgrowth however a singular course of pushed by particular tension-sensing cells.
“Our work offers new insights into the pathogenesis of keloids and opens the door to novel diagnostic and therapeutic strategies,” says Prof. Ikehara. “For example, PIEZO2 inhibitors, which are a type of calcium ion channel blocker, may help alleviate pain and itching associated with keloids. If such targeted therapies become clinically available, they could greatly improve the quality of life for patients suffering from keloid-related discomfort.”
Taken collectively, this examine contributes to the event of therapeutic methods to revive wholesome connective tissue, in the end bettering affected person outcomes.
Extra data:
Shinsuke Akita et al, Elevated expression of the PIEZO2 mechanoreceptor in fibroblasts and endothelial cells throughout the lymphatic and vascular vessels of keloids, The Journal of Pathology (2025). DOI: 10.1002/path.6455
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Researchers uncover a sort of fibroblast that will contribute to the formation and recurrence of overgrown scars (2025, October 8)
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