Localization and Regulation of Polymeric Ig Receptor in Healthy and Diseased Human Kidney
Autor: | Martin Johansson, Jenny Nyström, Karl Swärd, Helén Nilsson, David Lindgren, Krzysztof M. Krawczyk, Karin Leandersson |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_treatment 030232 urology & nephrology Apoptosis Plasma cell Kidney Pathology and Forensic Medicine Proinflammatory cytokine 03 medical and health sciences Young Adult 0302 clinical medicine Immune system medicine Humans Receptor Cells Cultured Aged Cell Proliferation urogenital system Chemistry Receptors Polymeric Immunoglobulin Kidney metabolism Epithelial Cells Middle Aged Prognosis Cell biology 030104 developmental biology medicine.anatomical_structure Cytokine Transcytosis Gene Expression Regulation Case-Control Studies Female Kidney Diseases Follow-Up Studies |
Zdroj: | The American journal of pathology. 189(10) |
ISSN: | 1525-2191 |
Popis: | The polymeric Ig receptor (PIgR) constitutes an important part of the immune system by mediating transcytosis of dimeric IgA into mucosal fluids. Although well studied in organs such as the intestine, the regulation and localization of PIgR in human kidney are incompletely characterized. Herein, using immunohistochemistry, we show that in healthy human kidneys, PIgR is expressed by the progenitor-like tubular scattered cells of the proximal tubules and by parietal epithelial cells of glomeruli. We further show that proximal tubular expression of PIgR becomes widespread during kidney disease, correlating to elevated levels of urinary secretory IgA. Urinary secretory IgA levels also correlated to the degree of tubular fibrosis, plasma creatinine, and urea levels. In addition, primary tubular cells were cultured to study the function and regulation of PIgR in vitro. Cellular PIgR expression was induced by conditioned medium from activated human leukocytes, as well as by inflammatory cytokines, whereas transforming growth factor-β1 caused decreased expression. Furthermore, interferon-γ increased the transcytosis of dimeric IgA in cultured tubular cells. Finally, a correlation study of mRNA data from the Genotype-Tissue Expression portal indicated that PIGR mRNA expression in kidney correlates to the expression of TNFSF13, a cytokine involved in plasma cell class switching to IgA. These results indicate that PIgR induction is an integral part of the injury phenotype of renal tubular cells. |
Databáze: | OpenAIRE |
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