Volumetric muscle loss (VML) causes irrecoverable loss of muscle mass and strength and results in permanent disability. VML injury shows extensive fibrosis, which impedes functional tissue regeneration. Our lab has created a biosponge scaffold composed of extracellular matrix (ECM) proteins (i.e., biosponge) that can enhance muscle regeneration and function following VML. In this work, a potent small molecule inhibitor of alpha v-subunit containing integrins known as IDL-2965 was incorporated into the biosponges for localized suppression of fibrosis post-VML. Our results demonstrate that local delivery of IDL-2965 via the biosponges attenuated the deposition of fibrotic tissue preceded by a downregulation of profibrotic genes in VML-injured muscles. The reduction in fibrotic tissue had no detrimental effects on muscle mass, function, size, or vascularity. Overall, these findings suggest that the codelivery of biosponges and IDL-2965 is a safe and effective strategy for the mitigation of fibrotic tissue deposition in VML-injured muscles.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajpcell.00092.2023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.
Acta Biomater
January 2025
Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA. Electronic address:
In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.
View Article and Find Full Text PDFModulation of γδ T cells by USF3: Implications for liver fibrosis and immune regulation.
Int Immunopharmacol
January 2025
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China. Electronic address:
Previous studies have established that γδ T cells play a significant role in liver fibrosis. However, their specific functions and mechanisms in fibrotic liver tissue remain unclear. Using online microarray expression profiles, we observed that USF3 was upregulated in patients with liver fibrosis and was associated with immune cells.
View Article and Find Full Text PDFMETTL3 Potentiates M2 Macrophage-Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF-β1/Smad3 Pathway.
Adv Sci (Weinh)
January 2025
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
METTL3, a key enzyme in N6-methyladenosine (m6A) modification, plays a crucial role in the progression of renal fibrosis, particularly in chronic active renal allograft rejection (CAR). This study explored the mechanisms by which METTL3 promotes renal allograft fibrosis, focusing on its role in the macrophage-to-myofibroblast transition (MMT). Using a comprehensive experimental approach, including TGF-β1-induced MMT cell models, METTL3 conditional knockout (METTL3 KO) mice, and renal biopsy samples from patients with CAR, the study investigates the involvement of METTL3/Smad3 axis in driving MMT and renal fibrosis during the episodes of CAR.
View Article and Find Full Text PDFTherapeutic Potential and Mechanistic Insights of a Novel Synthetic α-Lactalbumin-Derived Peptide for the Treatment of Liver Fibrosis.
J Clin Exp Hepatol
December 2024
Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt.
Background: Liver fibrosis is a serious global health issue, but current treatment options are limited due to a lack of approved therapies capable of preventing or reversing established fibrosis.
Aim: This study investigated the antifibrotic effects of a synthetic peptide derived from α-lactalbumin in a mouse model of thioacetamide (TAA)-induced liver fibrosis.
Methods: analyses were conducted to assess the physicochemical properties, pharmacophore features, and docking interactions of the peptide.
Alginate-polylysine-alginate (APA) microencapsulated transgenic human amniotic epithelial cells ameliorate fibrosis in hypertrophic scars.
Inflamm Res
January 2025
Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, No.127 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China.
Background: Hypertrophic scar (HS) is a severe skin fibrosis. Transplanting stem cells carrying anti-fibrotic cytokine genes, like interferon-gamma (IFN-γ), is a novel therapeutic strategy. Human amniotic epithelial cells (hAECs) are ideal seed cells and gene vectors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!