Emerging evidence reveals the importance of long non-coding RNAs (lncRNAs) in the development and progression of keloid formation, whereas the underlying mechanisms are not well understood. In the present study, we investigated the biological effects and molecular mechanisms of lncRNA HOXA11-AS in keloid formation. First, the expression levels of HOXA11-AS, miR-124-3p, and transforming growth factor β receptor type I (TGFβR1) were measured in both keloid tissues and human keloid fibroblasts (HKFs) using qRT-PCR and western blot analysis, respectively. Next, we adopted both gain- and loss-of-function strategies to explore the significance of HOXA11-AS. TUNEL, flow cytometry, DNA ladder, and tube formation assays were performed to measure cell apoptosis and angiogenesis, respectively. Besides, the potential binding relationship between HOXA11-AS and miR-124-3p, as well as miR-124-3p and TGFβR1 was identified using bioinformatic screening and verified by luciferase reporter assay. Furthermore, we explored the importance of miR-124-3p in HOXA11-AS-induced phenotypes and regulations on TGFβ signaling or PI3K/Akt signaling. We found that HOXA11-AS and TGFβR1 were significantly up-regulated, while miR-124-3p was down-regulated both in keloid tissues or fibroblasts than in normal skin tissues or fibroblasts. Functionally, high expression of HOXA11-AS essentially inhibited cell apoptosis and promoted fibroblast-induced angiogenesis. Mechanistically, miR-124-3p was identified as a downstream effector to be involved in HOXA11-AS-mediated phenotypes through directly targeting TGFβR1, thus modulating PI3K/Akt signaling pathway. Taken together, our findings revealed that HOXA11-AS inhibits cell apoptosis and promotes angiogenesis through miR-124-3p/TGFβR1 axis, contributing to the progression of keloid formation, which might provide a novel target for keloid therapy.
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http://dx.doi.org/10.1080/15384101.2019.1706921 | DOI Listing |
Front Immunol
January 2025
Dermatology Hospital, Southern Medical University, Guangzhou, China.
Background: Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases.
View Article and Find Full Text PDFJ Clin Med
January 2025
Thomas Jefferson SKMC, 1025 Walnut Street Suite 1100, Philadelphia, PA 19107, USA.
Urethral strictures and bladder neck contractures (BNCs) can be significantly morbid for patients and may require intervention for effective urinary drainage. We hypothesized patients with abnormal scarring disorders, such as keloids or hypertrophic scars, are at elevated risks of urethroplasty failure as well as postprocedural urethral strictures and BNCs. We queried the TriNetX database to determine the risk of urethroplasty failure for patients with abnormal scarring disorders compared to controls.
View Article and Find Full Text PDFFront Mol Biosci
January 2025
Department of Plastic Surgery, Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China.
Introduction: Keloids are a common skin disorder characterized by excessive fibrous tissue proliferation, which can significantly impact patients' health. Ferroptosis, a form of regulated cell death, plays a crucial role in the development of fibrosis; however, its role in the mechanisms of keloid formation remains poorly understood.
Methods: This study aimed to identify key genes associated with ferroptosis in keloid formation.
Burns Trauma
January 2025
Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Background: Keloids are disfiguring, fibrotic scar-like lesions that are challenging to treat and commonly recur after therapy. A deeper understanding of the mechanisms driving keloid formation is necessary for the development of more effective therapies. Reduced vitamin D receptor (VDR) expression has been observed in keloids, implicating vitamin D signaling in keloid pathology.
View Article and Find Full Text PDFCell Death Discov
January 2025
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as a mode of action for CD8T cell (CTL)-mediated keloid killing.
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