Cell Biology – Immunology – Pathology
Kidney International (1999) 55, 168–178; doi:10.1046/j.1523-1755.1999.00249.x
Bcl-2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation1
HSI-HUI LIN, TZI-PENG YANG, SI-TSE JIANG, HSI-YUAN YANG and MING-JER TANG
Departments of Physiology and Anatomy, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China
Correspondence: Ming-Jer Tang, M.D., Ph.D., Department of Physiology, National Cheng Kung University, Medical College, Tainan, Taiwan, R.O.C. E-mail: mjtang1@mail.ncku.edu.tw
1See Editorial, p. 334.
Received 17 April 1998; Revised 10 August 1998; Accepted 14 August 1998.
Abstract
Bcl-2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation.
Background
Madin-Darby canine kidney (MDCK) cells develop into simple epithelial cell cysts when cultured in type I collagen gel. We found that MDCK cells initially grow into multilayer cell aggregates and subsequently develop central lumen that contain apoptotic cells. We hypothesized that apoptosis might be essential for the formation of MDCK cysts.
Methods
Using MDCK cells cultured in collagen gel as the experimental model, we investigated how renal cells organize to form cysts. To delineate the role of apoptosis in the process of cyst formation, MDCK cells were transfected with the bcl-2 gene. Characterization of apoptosis was studied by morphological and biochemical methods.
Results
Bcl-2 overexpression conferred resistance to apoptosis. Cultured in collagen gel, Bcl-2 transfectants rarely formed a simple epithelial cyst, but instead remained as a multilayer cell aggregate containing central or multiple lumens, or even developing into branching structures.
Conclusions
Because Bcl-2 overexpression averts cyst cavitation, these data clearly indicate that apoptosis is an essential initial event for renal cyst formation.
Keywords:
renal cystic disease, apoptotic cells, programmed cell death, metanephros, polycystic kidney disease, ischemia
Abbreviations:
bcl-2, B-cell lymphoma-2; DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; HGF, hepatocyte growth factor; MDCK, Madin-Darby canine kidney; PBS, phosphate-buffered saline solution; uPA, urokinase-type plasminogen activator
