Background: In experimental extracapillary glomerulonephritis (EG) podocytes migrate, proliferate and change phenotype, and play a pivotal role in crescent formation. Hepatocyte Growth Factor (HGF) is an injury-induced effector of tissue repair that causes cell migration, growth and transdifferentiation via its receptor Met.
Methods: In 11 patients with EG we measured serum levels of HGF and investigated whether serum induces the release of HGF by Peripheral Blood Mononuclear Cells (PBMC). In renal biopsies we studied the expression of Met. In cultured podocytes we studied Met expression, migration, growth and morphological changes induced by recombinant (r) HGF.
Results: In patients with EG average serum levels of HGF (0.73 ng/ml) were higher than in normal volunteers (N, 0.10 ng/ml, p<0.01) and in patients with non-crescentic glomerular disease (GD, 0.18 ng/ml, p<0.01). Serum of EG induced a significant HGF release by PBMC (mean 0.58 ng/ml) in comparison with serum of N and GD (0.07 and 0.06 ng/ml, respectively, both p<0.001). Met was strongly expressed in crescents. Cultured podocytes expressed Met, and rHGF induced in podocytes a time- and dose-dependent migration, growth and epithelial to mesenchymal transdifferentiation.
Conclusions: These results suggest that HGF/Met system participates in the process of crescent formation by inducing podocyte migration, growth and mesenchymal transformation.
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http://dx.doi.org/10.1093/ndt/gfh740 | DOI Listing |
Int J Mol Med
March 2025
National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Cold‑inducible RNA‑binding protein (CIRP) is a cold shock protein implicated in the regulation of multiple biological processes depending on its cellular localization. However, to the best of our knowledge, the role of CIRP in liver regeneration and injury after hepatectomy has not been investigated. The present study was therefore designed to explore whether CIRP is involved in liver regeneration after hepatectomy and its specific role and underlying molecular mechanism.
View Article and Find Full Text PDFScience
January 2025
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.
View Article and Find Full Text PDFCell Rep
January 2025
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
Organisms allocate energetic resources between essential cellular processes to maintain homeostasis and, in turn, maximize fitness. The nutritional regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in Caenorhabditis elegans.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany, Cologne, North-rhine westphalia, Germany.
Background: Alzheimer's disease (AD) presents a prolonged asymptomatic phase, providing a significant timeframe for potential intervention. Leveraging this opportunity necessitates the early identification of diagnostic and prognostic biomarkers to detect Alzheimer's pathology during predementia stages. This enables the identification of individuals likely to progress to Alzheimer's-type dementia, allowing them to benefit from targeted disease-modifying therapies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Alzheimer's Disease Research Center, New York University Langone Health, New York, NY, USA.
Background: Cognitive impairment is one of the most frequently reported post-acute sequelae of COVID-19, yet the pathophysiology underpinning this symptom remains unknown. We aimed to explore the correlation of blood markers of inflammation, BBB disruption and neurodegeneration with MRI volume measurements in COVID-19 patients with and without cognitive impairment, and among patients with no prior history of COVID-19.
Method: We conducted a prospective study of COVID-19 patients (COV+; laboratory verified SARS-CoV-2 infection) and non-COVID-19 controls (COV-; no history of SARS-CoV-2 infection and negative SARS-CoV-2 nucleocapsid antibody).
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