Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease
Previous studies have highlighted epithelial proliferation and apoptosis in the cyst lining as common features in animal models of cystic disease. In this study, we sought to evaluate the timing and extent of these changes in renal tissue obtained from patients with autosomal-dominant, polycystic ki...
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Wiley
2007-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2007.274 |
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| author | Salwa Ibrahim |
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| author_sort | Salwa Ibrahim |
| collection | DOAJ |
| description | Previous studies have highlighted epithelial proliferation and apoptosis in the cyst lining as common features in animal models of cystic disease. In this study, we sought to evaluate the timing and extent of these changes in renal tissue obtained from patients with autosomal-dominant, polycystic kidney disease (ADPKD) subjected for nephrectomy for a variety of clinical indications. Cell proliferation was assessed using an antibody to proliferating cell nuclear antigen (PCNA), and apoptosis was evaluated by the use of terminal deoxynucleotidyl transferase (TdT) digoxigenin-deoxyuridine (dUTP) nick end-labeling technique (ApopTag®). The origin of cystic structures was evaluated using antibodies to epithelial membrane antigen (EMA). The lineage of interstitial mononuclear cells was assessed by anti CD 45 and CD 68 monoclonal antibodies. We found an increased rate of proliferation within the epithelium, not only of cystic, but also of noncystic, tubules that was significantly higher than the corresponding values from normal kidney (p ≤ 0.0001). Apoptotic index values were significantly increased within the epithelium lining noncystic and cystic structures (p < 0.001). In the interstitium, increased proliferation and apoptosis rates were also noted. Interstitial infiltrates were dense and consisted mainly of CD 68–positive macrophages and CD 45–positive lymphocytes. The present study demonstrated that changes in cell turnover are early events in cyst formation. The observation of mild proportionate elevation of both proliferation and apoptosis values of the epithelium lining cysts explains the lack of increase risk of renal cell carcinoma in ADPKD. The development of heavy interstitial inflammation could contribute to progressive tubulointerstitial scarring, leading to progressive renal failure. |
| format | Article |
| id | doaj-art-3357a301bb3241989ae3961dc84e4057 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2007-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-3357a301bb3241989ae3961dc84e40572025-02-03T05:45:56ZengWileyThe Scientific World Journal1537-744X2007-01-0171757176710.1100/tsw.2007.274Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney DiseaseSalwa Ibrahim0Department of Internal Medicine, Cairo University, EgyptPrevious studies have highlighted epithelial proliferation and apoptosis in the cyst lining as common features in animal models of cystic disease. In this study, we sought to evaluate the timing and extent of these changes in renal tissue obtained from patients with autosomal-dominant, polycystic kidney disease (ADPKD) subjected for nephrectomy for a variety of clinical indications. Cell proliferation was assessed using an antibody to proliferating cell nuclear antigen (PCNA), and apoptosis was evaluated by the use of terminal deoxynucleotidyl transferase (TdT) digoxigenin-deoxyuridine (dUTP) nick end-labeling technique (ApopTag®). The origin of cystic structures was evaluated using antibodies to epithelial membrane antigen (EMA). The lineage of interstitial mononuclear cells was assessed by anti CD 45 and CD 68 monoclonal antibodies. We found an increased rate of proliferation within the epithelium, not only of cystic, but also of noncystic, tubules that was significantly higher than the corresponding values from normal kidney (p ≤ 0.0001). Apoptotic index values were significantly increased within the epithelium lining noncystic and cystic structures (p < 0.001). In the interstitium, increased proliferation and apoptosis rates were also noted. Interstitial infiltrates were dense and consisted mainly of CD 68–positive macrophages and CD 45–positive lymphocytes. The present study demonstrated that changes in cell turnover are early events in cyst formation. The observation of mild proportionate elevation of both proliferation and apoptosis values of the epithelium lining cysts explains the lack of increase risk of renal cell carcinoma in ADPKD. The development of heavy interstitial inflammation could contribute to progressive tubulointerstitial scarring, leading to progressive renal failure.http://dx.doi.org/10.1100/tsw.2007.274 |
| spellingShingle | Salwa Ibrahim Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease The Scientific World Journal |
| title | Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease |
| title_full | Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease |
| title_fullStr | Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease |
| title_full_unstemmed | Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease |
| title_short | Increased Apoptosis and Proliferative Capacity are Early Events in Cyst Formation in Autosomal-Dominant, Polycystic Kidney Disease |
| title_sort | increased apoptosis and proliferative capacity are early events in cyst formation in autosomal dominant polycystic kidney disease |
| url | http://dx.doi.org/10.1100/tsw.2007.274 |
| work_keys_str_mv | AT salwaibrahim increasedapoptosisandproliferativecapacityareearlyeventsincystformationinautosomaldominantpolycystickidneydisease |