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- Title
TIMP-1 gene expression and PAI-1 antigen after unilateral ureteral obstruction in the adult male rat.
- Authors
Duymelinck, Carla; Dauwe, Simonne E.H.; De Greef, Kathleen E.J.; Ysebaert, Dirk K.; Verpooten, Gert A.; De Broe, Marc E.
- Abstract
TIMP-1 gene expression and PAI-1 antigen after unilateral ureteral obstruction in the adult male rat. Background. Sustained obstruction of urinary flow invariably leads to inflammation, loss of functional renal structures and progressive deposition of extracellular matrix proteins, culminating in renal fibrosis. Although increased renal tissue inhibitor of matrix metalloproteinase (TIMP-1) expression is one of the early events following experimental hydronephrosis, little is known about its cellular source. Both the recruited macrophage and the resident/recruited (myo)fibroblast have been postulated to be candidate TIMP-1 transcribing cells. Currently, data concerning plasminogen activator inhibitor type 1 (PAI-1) expression in the ligated kidney are unavailable. Our study concentrated on the localization of TIMP-1 expressing cells and PAI-1 immunoreactive cells in the obstructed rat kidney. Methods. Rats were sacrificed 1, 5, 10, 15, 20 and 26 days after unilateral ureteral obstruction (UUO) or sham-surgery (SOR). Leukocyte (OX-1+), macrophage (ED1+) and neutrophil infiltration were analyzed using specific antibodies or nuclear morphology. α-Smooth muscle actin (α-SMA) immunostaining was measured morphometrically. Mitotic figures and nuclei with an apoptotic morphology were quantified in hematoxylin-eosin (H&E)-stained sections. TIMP-1 mRNA transcribing cells were localized with in situ hybridization (ISH) and identified by subsequent immunostainings for α-SMA and macrophages. PAI-1 antigenicity was evaluated immunohistochemically in SOR, contralateral unobstructed kidneys (CUK), and UUO kidneys. Results. The number of leukocytes and macrophages in the ligated rat kidney increased progressively in time, starting from day 5 post-surgery when compared with CUKs. Neutrophil accumulation in UUO kidneys became apparent from day 5 and large intraluminal leukocyte clusters (neutrophils and macrophages) were found in the lumen of...
- Subjects
METALLOPROTEINASES; ANTIGENS; URETERIC obstruction
- Publication
Kidney International, 2000, Vol 58, Issue 3, p1186
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2000.00274.x