کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3884629 1249483 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calcimimetics inhibit renal pathology in rodent nephronophthisis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Calcimimetics inhibit renal pathology in rodent nephronophthisis
چکیده انگلیسی

The development and progression of renal cysts appears to be driven by reduced cellular calcium and increased cyclic adenosine monophosphate (cAMP) from G-protein-coupled receptors. To test whether treatment with a calcimimetic that stimulates the G-protein-coupled calcium-sensing receptor might normalize cystic epithelial cell intracellular calcium and cAMP, thereby inhibiting cyst progression, we used pcy mice. These animals develop cysts principally in the collecting duct, as do humans with nephronophthisis (NPHP). We administered the calcimimetic R-568 mixed in their food at early or late stages in the pathogenesis of cyst formation. The treatment reduced cyst enlargement, and the early treatment inhibited development of renal fibrosis. Although the effect of later treatment was more modest, both stages of the disease responded positively to treatment. Additionally, R-568 decreased total kidney cAMP in the pcy mice and, in vitro, decreased cAMP levels and cell proliferation, while increasing intracellular calcium in immortalized human autosomal recessive polycystic kidney disease renal epithelial cells. The latter two effects were unique to R-568 and not replicated by raising extracellular calcium. Thus, treating pcy mice with R-568 was effective in reducing cyst progression in this rodent model of NPHP. Direct studies will be needed to determine whether these results can be applied to the human disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 80, Issue 6, 2 September 2011, Pages 612–619
نویسندگان
, , , , , , , ,