Focal overexpression of collagen IV characterizes the initiation of epithelial changes in polycystic kidney disease.
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.
Schäfer
K
K
Institut für Anatomie und Zellbiologie 1, Universität Heidelberg, FRG.
Bader
M
M
Gretz
N
N
Oberbäumer
I
I
Bachmann
S
S
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
D012333:RNA, Messenger; D003094:Collagen