{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T16:49:56Z","timestamp":1776012596115,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms17060802","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T21:53:40Z","timestamp":1464126820000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Kidney Injury Molecule-1 Is Specifically Expressed in Cystically-Transformed Proximal Tubules of the PKD\/Mhm (cy\/+) Rat Model of Polycystic Kidney Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Stefan","family":"Gauer","sequence":"first","affiliation":[{"name":"Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Urbschat","sequence":"additional","affiliation":[{"name":"Department of Urology and Paediatric Urology, Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Gretz","sequence":"additional","affiliation":[{"name":"Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrid","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Kr\u00e4nzlin","sequence":"additional","affiliation":[{"name":"Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Geiger","sequence":"additional","affiliation":[{"name":"Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Oberm\u00fcller","sequence":"additional","affiliation":[{"name":"Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/pr.2013.191","article-title":"Pathophysiology of childhood polycystic kidney diseases: New insights into disease-specific therapy","volume":"75","author":"Sweeney","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/ki.2015.207","article-title":"A polycystin-centric view of cyst formation and disease: The polycystins revisited","volume":"88","author":"Ong","year":"2015","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.bbadis.2011.06.012","article-title":"Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD)","volume":"1812","author":"Norman","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ki.1994.253","article-title":"Characterization of the Han:SPRD rat model for hereditary polycystic kidney disease","volume":"46","author":"Gretz","year":"1994","journal-title":"Kidney Int."},{"key":"ref_5","first-page":"F357","article-title":"Differentiation and cell polarity during renal cyst formation in the Han:SPRD (cy\/+) rat, a model for ADPKD","volume":"273","author":"Obermuller","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/ndt\/11.supp6.46","article-title":"Rat models of autosomal dominant polycystic kidney disease","volume":"11","author":"Gretz","year":"1996","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1681\/ASN.2005060601","article-title":"Missense mutation in sterile alpha motif of novel protein samcystin is associated with polycystic kidney disease in (cy\/+) rat","volume":"16","author":"Brown","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/hmg\/6.4.609","article-title":"Location of the first genetic locus, PKDr1, controlling autosomal dominant polycystic kidney disease in Han:SPRD cy\/+ rat","volume":"6","author":"Bihoreau","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1046\/j.1523-1755.2002.00433.x","article-title":"Kidney injury molecule-1 (Kim-1): A novel biomarker for human renal proximal tubule injury","volume":"62","author":"Han","year":"2002","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1074\/jbc.273.7.4135","article-title":"Kidney injury molecule-1 (Kim-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury","volume":"273","author":"Ichimura","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F552","DOI":"10.1152\/ajprenal.00285.2002","article-title":"Kidney injury molecule-1: A tissue and urinary biomarker for nephrotoxicant-induced renal injury","volume":"286","author":"Ichimura","year":"2004","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_12","first-page":"293","article-title":"Kidney injury molecule-1: A translational journey","volume":"125","author":"Bonventre","year":"2014","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39739","DOI":"10.1074\/jbc.M200562200","article-title":"Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration","volume":"277","author":"Bailly","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/ajt.13087","article-title":"Tim-1 signaling is required for maintenance and induction of regulatory b cells","volume":"15","author":"Yeung","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1172\/JCI45361","article-title":"Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis","volume":"123","author":"Humphreys","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1681\/ASN.2004070530","article-title":"Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma","volume":"16","author":"Han","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nakagawa, S., Nishihara, K., Miyata, H., Shinke, H., Tomita, E., Kajiwara, M., Matsubara, T., Iehara, N., Igarashi, Y., and Yamada, H. (2015). Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136994"},{"key":"ref_18","first-page":"955","article-title":"Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans","volume":"141","author":"Ward","year":"1992","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1172\/JCI12980","article-title":"Osteopontin as a means to cope with environmental insults: Regulation of inflammation, tissue remodeling, and cell survival","volume":"107","author":"Denhardt","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"F1326","DOI":"10.1152\/ajprenal.00166.2002","article-title":"Kidney injury molecule-1 expression in murine polycystic kidney disease","volume":"283","author":"Kuehn","year":"2002","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(00)81570-6","article-title":"Somatic inactivation of PKD2 results in polycystic kidney disease","volume":"93","author":"Wu","year":"1998","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/1357-2725(95)00027-M","article-title":"Clusterin: Physiologic and pathophysiologic considerations","volume":"27","author":"Rosenberg","year":"1995","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S1357-2725(01)00155-8","article-title":"Clusterin","volume":"34","author":"Jones","year":"2002","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1046\/j.1523-1755.2001.00065.x","article-title":"Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats","volume":"60","author":"Cowley","year":"2001","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"C1225","DOI":"10.1152\/ajpcell.1992.263.6.C1225","article-title":"Localization of the chip28 water channel in rat kidney","volume":"263","author":"Sabolic","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F456","DOI":"10.1152\/ajprenal.00403.2005","article-title":"Tubular kidney injury molecule-1 in protein-overload nephropathy","volume":"291","author":"Bakker","year":"2006","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F313","DOI":"10.1152\/ajprenal.00180.2006","article-title":"Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase","volume":"292","author":"Vaidya","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44059","DOI":"10.18632\/oncotarget.6623","article-title":"Kim-1\/Tim-1 in proximal tubular cell immune response","volume":"6","author":"Brooks","year":"2015","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.15252\/embj.201489838","article-title":"Kim-1-\/Tim-1-mediated phagocytosis links ATG5-\/ULK1-dependent clearance of apoptotic cells to antigen presentation","volume":"34","author":"Brooks","year":"2015","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00467-015-3134-2","article-title":"Autophagy in renal diseases","volume":"31","author":"Decuypere","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_31","first-page":"2582","article-title":"A new rat model for polycystic kidney disease of humans","volume":"22","author":"Deerberg","year":"1990","journal-title":"Transplant. Proc."},{"key":"ref_32","unstructured":"Inbread Strains of Rat: PKD. Available online: http:\/\/www.informatics.jax.org\/external\/festing\/rat\/docs\/PKD.shtml."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ki.1996.426","article-title":"Thiazide treatment of rats provokes apoptosis in distal tubule cells","volume":"50","author":"Loffing","year":"1996","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1038\/ki.1995.222","article-title":"Expression of osteopontin, a urinary inhibitor of stone mineral crystal growth, in rat kidney","volume":"47","author":"Kleinman","year":"1995","journal-title":"Kidney Int."},{"key":"ref_35","first-page":"1","article-title":"Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney","volume":"129","author":"Grone","year":"1987","journal-title":"Am. J. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/6\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:24:26Z","timestamp":1760210666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/6\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,24]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["ijms17060802"],"URL":"https:\/\/doi.org\/10.3390\/ijms17060802","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,24]]}}}