Kidney transplantation is the preferred renal replacement therapy available. Yet, long-term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) - as a non-invasive source of information - were collected from 22 living donors and recipients. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longer-term graft adaptation. Complement activation was among the most dynamically regulated components. This unique atlas of the suEV proteome is provided through an online repository allowing dynamic interrogation by the user. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers - phosphoenol pyruvate carboxykinase (PCK2) - could be confirmed using targeted MS in an independent validation cohort of 22 additional patients. This study sheds light on the impact of kidney transplantation on urinary extracellular vesicle content and allows the first deduction of early molecular processes in transplant biology. Beyond that our data highlight the potential of suEVs as a source of biomarkers in this setting.
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http://dx.doi.org/10.1002/jev2.12026 | DOI Listing |
Int J Mol Sci
December 2024
Department of Physiology and Cell Biology, School of Medicine, University of Nevada Reno, Reno, NV 89557, USA.
The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders.
View Article and Find Full Text PDFMol Med
January 2025
Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Background: Chronic kidney disease (CKD) is a leading cause of death in the United States, and renal fibrosis represents a pathologic hallmark of CKD. Extracellular cold-inducible RNA-binding protein (eCIRP) is a stress response protein involved in acute inflammation, tissue injury and regulated cell death. However, the role of eCIRP in chronic inflammation and tissue injury has not been elucidated.
View Article and Find Full Text PDFVirulence
December 2025
Henan International Joint Laboratory of Children's Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
is a gram-negative pathogen that can cause multiple diseases including sepsis, urinary tract infections, and pneumonia. The escalating detections of hypervirulent and antibiotic-resistant isolates are giving rise to growing public concerns. Outer membrane vesicles (OMVs) are spherical vesicles containing bioactive substances including lipopolysaccharides, peptidoglycans, periplasmic and cytoplasmic proteins, and nucleic acids.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Basic Medical Sciences, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Background: The partial epithelial-mesenchymal transition (EMT) is emerging as a significant mechanism in diabetic nephropathy (DN). LOX is a copper amine oxidase conventionally thought to act by crosslinking collagen. However, the role of LOX in partial EMT and fibrotic progression in diabetic nephropathy has not been investigated experimentally.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008.
Renal fibrosis is the common pathological basis for the progressive development of chronic kidney disease (CKD) caused by various etiologies. It is characterized by the persistent deposition of extracellular matrix, leading to renal tissue damage and impaired renal function, and ultimately progressing to kidney failure. Current clinical treatments for CKD mainly focus on managing the primary diseases, with no specific drugs targeting renal fibrosis.
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