Neonatal Fc receptor stimulation induces ubiquitin c-terminal hydrolase-1 overexpression in podocytes through activation of p38 mitogen-activated protein kinase

• Published in: Human pathology 2012-09, Vol.43 (9), p.1482-1490
• Main Authors: Gan, Hualei, PhD, Feng, Songtao, PhD, Wu, Huijuan, PhD, Sun, Yu, MD, Hu, Ruimin, MD, Zhao, Zhonghua, PhD, Zhang, Zhigang, PhD
• Format: Article
• Language: English
• Subjects: Animals; Antilymphocyte Serum - pharmacology; Binding sites; Biological and medical sciences; Cell culture; Cell Line; Cells, Cultured; Glomerulonephritides; Histocompatibility Antigens Class I - metabolism; Humans; Investigative techniques, diagnostic techniques (general aspects); Kidney - drug effects; Kidney - immunology; Kidney - metabolism; Kidney Diseases - immunology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidneys; Kinases; Medical sciences; Mice; Neonatal Fc receptor; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Pathogenesis; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phosphorylation; Podocyte; Podocytes - drug effects; Podocytes - immunology; Podocytes - metabolism; Proteins; Receptors, Fc - metabolism; Rodents; Signal Transduction - drug effects; Signal Transduction - physiology; T-Lymphocytes - immunology; Ubiquitin c-terminal hydrolase-1 (UCH-L1); Ubiquitin Thiolesterase - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2011.10.025

Summary Ubiquitin c-terminal hydrolase-1 is overexpressed in renal podocytes in some immune complex-mediated glomerulonephritides, an effect closely related to extensive podocyte injury. Neonatal Fc receptor is newly recognized to be present on human renal podocytes. It is presumed that neonatal Fc receptor serves as a sensor for immune stimulation transduction and is involved in the pathogenesis of podocyte injury. In our current study, we found that neonatal Fc receptor was constitutively expressed in normal podocytes and up-regulated by immune stimulation induced by antithymocyte serum. An increase in neonatal Fc receptor expression was observed in human podocytes within diseased glomeruli in 97 cases of various glomerulonephritides. The expression percentage was significantly higher in immune-mediated disease, including membranous nephropathy (46.7%), immunoglobin A nephropathy (66.7%), lupus nephritis (87.5%), and acute proliferative glomerulonephritis (100%), than in normal kidney samples (16.7%) ( P < .05), whereas there was no significant difference between minimal-change disease and normal kidney. Further study showed that neonatal Fc receptor up-regulated the expression of ubiquitin c-terminal hydrolase-1 via activation of p38 in podocytes subjected to immune stimulation in vitro. These data suggest that neonatal Fc receptor acts as an immune sensor that evokes an inflammatory response, which may lead to functional and morphological changes in podocytes in glomerulonephritides.