| Summary: | 碩士 === 長榮大學 === 醫學研究所 === 94 === Autosomal dominant polycystic kidney disease (ADPKD) has an incidence of 1 in 1000 live births. It is the most common life-threatening inherited cystic kidney diseases characterized by the development of gradually enlarging renal cysts and a progressive loss of normal renal tissue that can lead to chronic renal failure and hemodialysis. Finding of PKD1 and PKD2 genes were major milestones in studying of this specific kidney disease. ADPKD is recognized as a monogenic disorder caused by mutation in two genes, PKD1, accounting for approximately 85% - 90％ of cases, and PKD2, accounting for approximately 10% of cases. Polycystin-1（pkd-1） and polycystin-2（pkd-2） are the proteins of these two genes. Polycystin-1 is a large (>460 KD) membrane protein of about 4300 amino acids with 11 transmembrane domains. Its extensive extracellular N terminus contains a number of adhesive domains that implicate polycystin-1 in cell-cell and cell-matrix interactions. Their functions include cell proliferation, regulation of cell survival, altered tubular cell polarity, fluid secretion, and reaction with extracellular matrix. In our preliminary data, renal tubular cystic epithelium was noted to have a tendency to detach from extracellular matrix. Meanwhile, in renal tissue of cDNA microarray analysis, laminin γ3 upregulated also was noted. About this reason, our purposes will focus on the role of laminin γ3 , element of ECM, in the developmental process of renal cystic formation and the interaction between extracellular matrix abnormalities and PKD disease. That utilizes critical information gained from this genetically manipulated mouse models for the purpose of aberrant expression of laminin γ3 . Overall, in homozygous mutant, the distribution aberrant of laminin γ3 translocated from basement to apical side at day 1 and the expression of laminin γ3 was increased at day 30. Meanwhile, the expression of laminin γ3 and polycystin-1 protein is colocalized in either cytoplasm or apical side of congenital ADPKD mice.
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