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Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease, and podocyte injury is an important factor in the development of DKD. Mitophagy is severely inhibited in the podocytes of patients. Damaged mitochondria aggregate in the cytoplasm and can not be removed effectively. Restoring mitophagy may be a novel strategy for the treatment of DKD. In this study, Regulatory T cells (Tregs) are found to reduce podocyte injury in DKD through exosomes. Sequencing and cross-sectional analysis revealed that exosomes from Tregs delivered miR-218-5p to increase mitophagy in podocytes by inhibiting the TNC/TLR4/SRC/FUNDC1 pathway. Treg-Exos are engineered to express RGD peptides on the membrane surface. RGD-Treg-Exos bind to integrins on the surface of podocytes and effectively target podocytes for the delivery of miR-218-5p, thus increasing mitophagy in podocytes, reducing cell apoptosis, and alleviating podocyte injury. In summary, this study revealed that engineered RGD-Treg-Exos effectively ameliorated podocyte injury in DKD, thus constituting a novel method for DKD treatment.
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http://dx.doi.org/10.1002/advs.202412034 | DOI Listing |
Clin Chim Acta
September 2025
Department of Physiology, University of Louisville, Louisville 40202 KY, USA. Electronic address:
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, with podocyte injury representing an early pathogenic event. Conventional biomarkers such as albuminuria and eGFR identify renal damage only at advanced stages, limiting opportunities for timely intervention. Wilms' Tumor 1 (WT1), a podocyte-specific transcription factor, has emerged as a sensitive marker of early glomerular stress.
View Article and Find Full Text PDFGen Physiol Biophys
September 2025
The Second Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Diabetic nephropathy (DN) is a major complication of diabetes, imposing substantial socioeconomic and public health challenges. N6-methyladenosine (m6A) modification, a prevalent epigenetic mechanism, influences cellular processes and disease progression. Wilms' tumor 1-associating protein (WTAP), an m6A methyltransferase subunit, was investigated for its role in DN.
View Article and Find Full Text PDFCureus
August 2025
Department of Nephrology, Georgian American University, Tbilisi, GEO.
This case report describes a 38-year-old female patient with type 1 diabetes who developed collapsing-type glomerulonephritis (CTGN), a rare but severe kidney injury. The patient presented with nephrotic syndrome symptoms, including edema and hypertension. Laboratory tests showed significant proteinuria with normal serum creatinine and glomerular filtration rate.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Nephrology, Chungnam National University, Daejeon, Republic of Korea.
Diabetic kidney disease (DKD) involves oxidative stress-driven damage to glomeruli (Gloms) and proximal convoluted tubules (PCT). NAD(P)H: quinone oxidoreductase 1 (NQO1) regulates redox balance, but its compartment-specific role remains unclear. Streptozotocin (STZ)-induced hyperglycemia increased albuminuria and foot process effacement, with NQO1 KO (NKO) mice exhibiting greater podocyte injury than WT, indicating exacerbated glomerular damage.
View Article and Find Full Text PDFEvol Med Public Health
August 2025
Department of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Primitive emunctory functions to expel harmful substances from cells and the interstitial space of multicellular organisms evolved over the past billion and a half years into the complex physiology of the metanephric kidney. Integrative biology allows empirical testing of hypotheses of the origins of renal structures from homologous single-celled precursors. Emunctory cell complexes called nephridia evolved in metazoan (cnidarian) ancestors 750 million years ago (mya).
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