The use of stem cells capable of multilineage differentiation in treating Pelvic Floor Dysfunction (PFD) holds great promise since they are susceptible to entering connective tissue of various cell types and repairing damaged tissues. This research investigated the effect of microRNA-181a-5p (miR-181a-5p) on Bone Marrow Mesenchymal Stem Cells (BMSCs) in rats with PFD. BMSCs were transfected and analyzed for their fibroblast differentiation ability. miR-181a-5p, MFN1, and fibroblast-related genes were quantitatively analyzed. Whether MFN1 is a target gene of miR-181a-5p was predicted and confirmed. The efficacy of BMSCs in vivo rats with PFD was evaluated by measuring Leak Point Pressure (LPP), Conscious Cystometry (CMG), hematoxylin and eosin staining, and Masson staining. The present results discovered that miR-181a-5p was up-regulated and MFN1 was down-regulated during the differentiation of BMSCs into fibroblasts. Fibroblast differentiation of BMSCs was promoted after miR-181a-5p was induced or MFN1 was suppressed, but it was suppressed after miR-181a-5p was silenced. miR-181a-5p improved LPP and conscious CMG outcomes in PDF rats by targeting MFN1 expression, thereby accelerating fibroblast differentiation of BMSCs. In brief, miR-181a-5p induces fibroblast differentiation of BMSCs in PDF rats by MFN1, potentially targeting PDF therapeutics.
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http://dx.doi.org/10.1016/j.clinsp.2024.100428 | DOI Listing |
Heliyon
January 2025
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Our previous studies indicate that NFI-C is essential for tooth root development and endochondral ossification. However, its exact role in calvarial intramembranous bone formation remains unclear. In this study, we demonstrate that the disruption of the gene leads to defects in intramembranous bone formation, characterized by decreased osteogenic proliferative activity and reduced osteoblast differentiation during postnatal osteogenesis.
View Article and Find Full Text PDFFront Neurol
January 2025
14th European Reference Network in Neuromuscular Disorders (EURO-NMD), Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia.
Background: Charcot-Marie-Tooth disease (CMT), a slowly advancing hereditary nerve disorder, presents a significant challenge in the medical field. Effective drugs for treatment are lacking, and we struggle to find sensitive markers to track the disease's severity and progression. In this study, our objective was to investigate the levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) in individuals with CMT and to compare them to a control group.
View Article and Find Full Text PDFJ Invest Dermatol
January 2025
Centre for Gene Therapy and Regenerative Medicine, King's College London, Guy's Hospital, Great Maze Pond, London, UK; Directors' Unit, EMBL, Meyerhofstr. 1, 69117 Heidelberg, Germany. Electronic address: https://twitter.com/fionamarywatt.
To investigate heterogeneity of fibroblasts in human fetal skin, we analysed published single-cell RNA sequencing data (8 and 16 post conception weeks (PCW)) and performed single-molecule fluorescence in situ hybridisation to map their spatial distribution and predicted dynamic interactions. Clustering revealed 8 fibroblast populations with developmental stage-specific abundance changes. Proliferative cells (MKI67+) were present at all stages.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, 621 Gangwan Road, Huangpu District, Guangzhou, Guangdong, 510799, China.
Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency.
View Article and Find Full Text PDFHGG Adv
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA; University Program in Genetics and Genomics, Duke University, Durham, NC, USA; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Electronic address:
Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.
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