title: Exposure to nephrotoxic ochratoxin A enhances collagen secretion in human renal proximal tubular cells.
abstract: Ochratoxin A (OTA) is a nephrotoxic mycotoxin. There is evidence that OTA leads to cortical interstitial nephropathies in humans, associated with fibrosis. No data are available on the effect of OTA-induced collagen secretion from renal cortical cells. As kidney cortex mainly consists of proximal tubules, we investigated the effect of OTA on particular collagens (I, III, IV) in a well-established proximal tubular cell line (opossum kidney (OK) cells) and in primary cultured human renal proximal tubular epithelial cells (RPTECs). In fibroblasts, OTA neither exerted toxic effects nor induced collagen secretion, most probably due to the absence of suitable uptake mechanisms. OTA exerted time- and dose-dependent toxicity in both OK cells and human RPTECs. Moreover, OTA induced collagen secretion in a time- and dose-dependent manner in both cell types. In opposite to transforming growth factor beta1 (TGF-beta1), OTA incubation induced increased apical secretion of the basement membrane collagen IV. This might be evidence for a loss of cellular polarity after OTA incubation. We conclude that in proximal tubular cells, OTA is able to induce extracellular matrix deposition. As collagen secretion was also inducible in primary cultured human RPTECs, we hypothesize that OTA-induced extracellular matrix deposition by proximal tubular cells may be of importance in generation of renal diseases in humans which are under suspicion of being induced by OTA.
authors.affiliation: Physiologisches Institut, Universität Würzburg, Würzburg, Germany. christoph.sauvant@mail.uni-wuerzburg.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Sauvant
authors.forename: Hildegard
authors.initials: H
authors.lastname: Holzinger
authors.forename: Sigrid
authors.initials: S
authors.lastname: Mildenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Gekle
mesh_terms: D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D009793:Ochratoxins / Q000008:administration & dosage / Q000633:toxicity*; D009893:Opossums; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D009793:Ochratoxins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C025589:ochratoxin A; D003094:Collagen