Gene expression and cell turnover in human renal dysplasia

Kidney malformations are common causes of chronic renal failure in children . Dysplastic kidneys represent a unique model of perturbed epithelial-mesen chymal interaction which leads to the formation of malformed branching tubu les surrounded by undifferentiated and metaplastic mesenchymal cells. We ha ve found that human dysplastic epithelia express PAX2 (a transcription fact or), BCL2 (a survival factor) and galectin-3 (a cell adhesion/signaling mol ecule). These genes are implicated in oncogenesis and their persistent expr ession may drive proliferation of dysplastic cysts, hence explaining the ma ssive growth of some multicystic dysplastic kidneys. We have also detected prominent apoptosis in undifferentiated tissues around dysplastic epithelia , and this may provide a potential mechanism for the well-documented regres sion of dysplastic kidneys. Hence, although these kidneys may not have any excretory function, it is incorrect to consider them as 'end stage organs' because they are highly active in terms of cell turnover and gene expressio n; furthermore, these processes can be correlated with patterns of tissue g rowth and involution. Further elucidation of 'molecular lesions' in renal m alformations may lead to novel therapies to enhance the differentiation of progenitor cells.