کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8944342 | 1645242 | 2018 | 51 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Abnormal Morphology of Distal Tubular Epithelial Cells Is Regulated by Genetic Factors Derived from Mouse Chromosome 12
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موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
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چکیده انگلیسی
The distal tubule (DT) helps regulate blood pressure and electrolytes. We describe a novel, autosomal recessive, morphofunctional DT abnormality in inbred mice evident as columnar alternations and age-related cystic changes. This abnormality developed in both sexes of DBA/2Cr. Similar phenotypes were observed in A/J, C3H/He, DBA/1J, and FVB/N strains, but not in AKR/N, BALB/c, or C57BL/6N strains. In DBA/2Cr, abnormal DT localized to straight and convoluted segments and showed IL-36α DT injury marker expression. However, DT epithelial proliferation, examined by bromodeoxyuridine incorporation, was not remarkably altered with the progression of abnormality. Abnormal DT epithelial cells in DBA/2Cr displayed elongated primary cilia, loose intercellular adhesions, and numerous vesicles with altered localization of CD9, Na+/K+ATPase, and E-cadherin, indicating altered cell function, adhesion, and polarity. DBA/2Cr-type D12Mit182-D12Mit83 was identified as a candidate locus designated DBA/2 renal cyst (drecy). Within drecy, the gene regulated by estrogen in breast cancer protein (Greb1) transcript variant 2 was significantly up-regulated in DBA/2Cr kidney versus C57BL/6N. Greb1 localized to DT cytoplasm in C57BL/6 and to cytoplasm and nucleus in DBA/2Cr. Greb1-overexpressing M-1 kidney cells showed an altered epithelial-mesenchyme phenotype. B6.D2-(D12Mit182-D12Mit83) congenic mice carrying drecy did not show DT abnormalities, whereas DBA/2Cr à B6.D2-(D12Mit182-D12Mit83) mice did. Identification of this novel DT abnormality regulated by a DBA/2Cr mouse chromosome 12-derived locus and additional genetic factors improve the understanding of DT pathogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 188, Issue 9, September 2018, Pages 2120-2138
Journal: The American Journal of Pathology - Volume 188, Issue 9, September 2018, Pages 2120-2138
نویسندگان
Osamu Ichii, Teppei Nakamura, Taro Horino, Akira Yabuki, Yaser H.A. Elewa, Yasuhiro Kon,