کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3886637 1249555 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parathyroid hormone-related protein promotes inflammation in the kidney with an obstructed ureter
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Parathyroid hormone-related protein promotes inflammation in the kidney with an obstructed ureter
چکیده انگلیسی

Parathyroid hormone-related protein (PTHrP) promotes fibrogenesis in the acutely damaged kidney. Considering the relation between fibrosis and inflammation, we studied transgenic mice that overexpress PTHrP in the proximal tubule. When unilateral ureteric obstruction was induced in these transgenic mice, we found that they had more renal tubulointerstitial damage, leukocyte influx, and expression of proinflammatory factors than their control littermates. Reversal of PTHrP constitutive overexpression in these transgenic mice or treatment of control mice with the PTHrP antagonist (7–34) decreased this inflammatory response. Losartan, which abolished obstruction-induced endogenous PTHrP upregulation, also decreased the latter response but less effectively in transgenic mice. The PTHrP fragment (1–36) induced nuclear factor-κB (NF-κB) activation and proinflammatory cytokine overexpression in mouse cortical tubule cells in culture as well as migration of the macrophage cell line Raw 264.7. All these effects were decreased by PTHrP (7–34) and NF-κB or extracellular signal-regulated kinase (ERK) activation inhibitors. Our findings suggest a critical role of PTHrP in the renal inflammatory process that results from ureteral obstruction and indicate that ERK-mediated NF-κB activation seems to be an important mechanism whereby PTHrP triggers renal inflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 73, Issue 7, 1 April 2008, Pages 835–847
نویسندگان
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