title: Expression of prorenin receptor in renal biopsies from patients with IgA nephropathy.
abstract: Prorenin receptor (PRR) has been implicated in the onset and progression of various renal diseases, though its possible association with immunoglobulin A (IgA) nephropathy remains unclear. In the present study, we tried to clarify expression and pathophysiological significance of PRR in IgA nephropathy. We immunohistochemically assessed PRR levels in renal biopsy specimens from 48 patients with IgA nephropathy and evaluated its relevance to the clinical and pathological features of the disease. PRR was detected mainly in renal tubular cells, which was confirmed at the subcellular level using immunoelectron microscopy. The PRR-positive area (%PRR area) correlated with daily urinary protein, which is known to reflect disease severity (r=0.286, P=0.049). PRR levels were weaker in tubular cells bordering areas of severe interstitial fibrosis, where α-smooth muscle actin-positive myofibroblasts were present. We also used immunohistochemical detection of microtubule-associated protein-1 light chain 3 (LC3) and electron microscopy to assess autophagy, a cytoprotective mechanism downstream of PRR. We noted an apparent coincidence between autophagy activation in tubular cells and PRR expression in the same cells. Taken together, our findings suggest that renal expression of PRR in IgA nephropathy may be a compensatory response slowing disease progression by preventing tubular cell death and subsequent fibrosis through activation of cytoprotective autophagic machinery. Further studies using different type of kidney diseases could draw conclusion if the present finding is a generalized observation beyond IgA nephropathy.
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Miyazaki
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Ichijiro
authors.initials: I
authors.lastname: Murata
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan ; Department of Internal Medicine, Asahi University Mizuho, Gifu, Japan.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Matsumoto-Miyazaki
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Gakuro
authors.initials: G
authors.lastname: Yoshida
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan ; Division of Nephrology, Murakami Memorial Hospital Asahi University Gifu, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kashi
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Niimi
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Ayuko
authors.initials: A
authors.lastname: Nishiwaki
authors.affiliation: Pathology Division, Gifu University Hospital Gifu, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Division of Nephrology, Murakami Memorial Hospital Asahi University Gifu, Japan.
authors.forename: Michiya
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Division of Nephrology, Murakami Memorial Hospital Asahi University Gifu, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Ohashi
authors.affiliation: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University Gifu, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Second Department of Internal Medicine, Gifu University Graduate School of Medicine Gifu, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009392:Nephrectomy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D055815:Young Adult; D000093342:Prorenin Receptor
chemical_list: D008869:Microtubule-Associated Proteins; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor
keywords: IgA nephropathy; prorenin receptor; renal biopsy