title: Focal overexpression of collagen IV characterizes the initiation of epithelial changes in polycystic kidney disease.
abstract: Changes of extracellular matrix are involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The relationship between epithelial changes and extracellular matrix production was studied in a new rat model (Han:SPRD/cy+) at an early phase of cystogenesis. Messenger RNA expression of the alpha 1(IV)-chain of collagen type IV, the main structural component of basement membrane, was localized by in situ hybridization. The presence of collagen IV-protein was shown by immunohistochemistry. At an initial stage, cysts were lined with normal-appearing epithelium except for focal zones of less differentiated cells exhibiting strong collagen alpha 1(IV) mRNA expression and a thickened basement membrane. In these zones, an increase in cell number (2.39-fold) per unit epithelial area indicated hyperplastic growth. Conspicuously, these zones were found at 'bottleneck'-like transitions from normal-size tubules to cystic expansions. Intermediate stages of cysts showed more prominent extracellular matrix deposits and an overall maximally enhanced collagen IV mRNA expression, whereas terminal stages were lined with a flat, simplified epithelium and exhibited moderate collagen IV expression. We suggest that focally enhanced expression of collagen IV in the tubular epithelium and surrounding interstitium of Han:SPRD/cy+ rat kidney is initially involved in cyst development.
authors.affiliation: Institut für Anatomie und Zellbiologie 1, Universität Heidelberg, FRG.
authors.forename: K
authors.initials: K
authors.lastname: Schäfer
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: N
authors.initials: N
authors.lastname: Gretz
authors.forename: I
authors.initials: I
authors.lastname: Oberbäumer
authors.forename: S
authors.initials: S
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D003094:Collagen