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

  • 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.

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Metadaten
Author:Stefan GauerGND, Anja UrbschatORCiDGND, Norbert Gretz, Sigrid C. Hoffmann, Bettina Kränzlin, Helmut GeigerGND, Nicholas ObermüllerGND
URN:urn:nbn:de:hebis:30:3-430022
DOI:https://doi.org/10.3390/ijms17060802
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/27231899
Parent Title (English):International Journal of Molecular Sciences
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2016/05/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/03/14
Tag:Kim-1; dedifferentiation; polycystic kidney; proximal tubule; rat model
Volume:17
Issue:Heft 6, Nr. 802
HeBIS-PPN:450780546
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0