Objective: Diabetic nephropathy (DN) represents the most common diabetic complication that may lead to end-stage renal disease. This work focused on the effect of FOXA1 on the DN development and the molecular mechanism.
Methods: A mouse model of DN was induced by high-fat diets and streptozotocin. The concentrations of blood glucose and urinary protein in mice, and the pathological changes in mouse kidney tissues were determined. A podocyte cell line MPC-5 was treated with high glucose (HG) to mimic a DN-like condition in vitro. FOXA1 and SATB1 were overexpressed in HG-treated MPC-5 cells and in DN mice to explore their effects on cell proliferation and apoptosis, and on pathological changes in mouse kidney tissues. The binding relationship between FOXA1 and STAB1 was predicted and validated. Activation of the Wnt/β-catenin pathway was detected.
Results: FOXA1 was poorly expressed in the kidney tissues of DN mice. Overexpression of FOXA1 reduced the concentrations of fasting blood glucose and 24-h urinary protein in mice. It also suppressed the accumulation of glomerular mesangial matrix and hyperplasia of glomerular basement membrane, and reduced collagen deposition and interstitial fibrosis in mouse kidney. Also, FOXA1 reduced HG-induced apoptosis of MPC-5 cells. FOXA1 bound to the promoter region of SATB1 for transcription suppression. Overexpression of SATB1 activated the Wnt/β-catenin pathway and blocked the protective roles of FOXA1 in DN mice and in HG-treated MPC-5 cells.
Conclusion: This study demonstrated that FOXA1 transcriptionally suppresses SATB1 expression and inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting podocyte apoptosis and DN progression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439979 | PMC |
| http://dx.doi.org/10.2147/DMSO.S314709 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Decoding the Role of Kinesin Superfamily Proteins in Glioma Progression.
J Mol Neurosci
January 2025
Gilgamesh Ahliya University, Baghdad, Iraq.
Glioma is a highly aggressive and invasive brain tumor with limited treatment options, highlighting the need for novel therapeutic approaches. Kinesin superfamily proteins (KIFs) are a diverse group of motor proteins that play essential roles in cellular processes such as mitosis, intracellular transport, and signal transduction, all of which are crucial for tumorigenesis. This review focuses on the multifaceted role of KIFs in glioma, examining their clinical relevance, contribution to tumor progression, and potential as therapeutic targets.
View Article and Find Full Text PDFIntegrative Analysis of Whole-Genome and Transcriptomic Data Reveals Novel Variants in Differentially Expressed Long Noncoding RNAs Associated with Asthenozoospermia.
Noncoding RNA
January 2025
Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece.
: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Emerging evidence suggests that noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play a critical role in the regulation of spermatogenesis and sperm function. Coding regions have a well-characterized role and established predictive value in asthenozoospermia.
View Article and Find Full Text PDFBillion-Scale Expansion of Functional hiPSC-Derived Cardiomyocytes in Bioreactors Through Oxygen Control and Continuous Wnt Activation.
Adv Sci (Weinh)
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2780901, Portugal.
Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB.
View Article and Find Full Text PDFImproved Black Phosphorus Nanocomposite Hydrogel for Bone Defect Repairing: Mechanisms for Advancing Osteogenesis.
Adv Healthc Mater
January 2025
Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, Jinan, Shandong, 250012, China.
Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair and regeneration. Bone tissue engineering is emerging as a promising alternative to traditional therapies like autografts and allografts.
View Article and Find Full Text PDFViscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats.
Regen Biomater
November 2024
Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215000, PR China.
A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous.
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!