Kidney injury molecule-1 is specifically expressed in cystically-transformed proximal tubules of the PKD/Mhm (cy/+) rat model of polycystic kidney disease

• Verfasst von: Gauer, Stefan [VerfasserIn]
• Verfasst von: Gretz, Norbert [VerfasserIn]
• Verfasst von: Hoffmann, Sigrid [VerfasserIn]
• Verfasst von: Kränzlin, Bettina [VerfasserIn]
• Titel: Kidney injury molecule-1 is specifically expressed in cystically-transformed proximal tubules of the PKD/Mhm (cy/+) rat model of polycystic kidney disease
• Verf.angabe: Stefan Gauer, Anja Urbschat, Norbert Gretz, Sigrid C. Hoffmann, Bettina Kränzlin, Helmut Geiger and Nicholas Obermüller
• E-Jahr: 2016
• Jahr: 24 May 2016
• Umfang: 12 S.
• Fussnoten: Gesehen am 17.06.2019
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2016
• Band/Heft Quelle: 17(2016,6) Artikel-Nummer 802, 12 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms17060802
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: dedifferentiation
• Sach-SW: Kim-1
• Sach-SW: polycystic kidney
• Sach-SW: proximal tubule
• Sach-SW: rat model
• K10plus-PPN: 1667533665

Abstract

Expression of kidney injury molecule-1 (Kim-1) is rapidly upregulated following tubular injury, constituting a biomarker for acute kidney damage. We examined the renal localization of Kim-1 expression in PKD/Mhm (polycystic kidney disease, Mannheim) (cy/+) rats (cy: mutated allel, +: wild type allel), an established model for autosomal dominant polycystic kidney disease, with chronic, mainly proximal tubulointerstitial alterations. For immunohistochemistry or Western blot analysis, kidneys of male adult heterozygously-affected (cy/+) and unaffected (+/+) littermates were perfusion-fixed or directly removed. Kim-1 expression was determined using peroxidase- or fluorescence-linked immunohistochemistry (alone or in combination with markers for tubule segments or differentiation). Compared to (+/+), only in (cy/+) kidneys, a chronic expression of Kim-1 could be detected by Western blot analysis, which was histologically confined to an apical cellular localization in areas of cystically-transformed proximal tubules with varying size and morphology, but not in distal tubular segments. Kim-1 was expressed by cystic epithelia exhibiting varying extents of dedifferentiation, as shown by double labeling with aquaporin-1, vimentin or osteopontin, yielding partial cellular coexpression. In this model, in contrast to other known molecules indicating renal injury and/or repair mechanisms, the chronic renal expression of Kim-1 is strictly confined to proximal cysts. Its exact role in interfering with tubulo-interstitial alterations in polycystic kidney disease warrants future investigations.