التفاصيل البيبلوغرافية
| العنوان: |
Blockade of KCa3.1 Ameliorates Renal Fibrosis Through the TGF-β1/Smad Pathway in Diabetic Mice. |
| المؤلفون: |
Chunling Huang, Shen, Sylvie, Qing Ma, Chen, Jason, Gill, Anthony, Pollock, Carol A., Xin-Ming Chen |
| المصدر: |
Diabetes; Aug2013, Vol. 62 Issue 8, p2923-2934, 12p, 4 Color Photographs, 3 Charts, 1 Graph |
| مصطلحات موضوعية: |
CALCIUM-dependent potassium channels, RENAL fibrosis, DIABETIC nephropathies, LABORATORY mice, NITRIC-oxide synthases, ALBUMINS, CREATININE, MONOCYTE chemotactic factor |
| مستخلص: |
The Ca2+-activated K+ channel KCa3.1 mediates cellular signaling processes associated with dysfunction of vasculature. However, the role of KCa3.1 in diabetic nephropathy is unknown. We sought to assess whether KCa3.1 mediates the development of renal fibrosis in two animal models of diabetic nephropathy. Wild-type and KCa3.1-/- mice, and secondly eNOS-/- mice, had diabetes induced with streptozotocin and then were treated with/without a selective inhibitor of KCa3.1 (TRAM34). Our results show that the albumin-to-creatinine ratio significantly decreased in diabetic KCa3.1-/- mice compared with diabetic wild-type mice and in diabetic eNOS-/- mice treated with TRAM34 compared with diabetic mice. The expression of monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule 1 (ICAM1), F4/80, plasminogen activator inhibitor type 1 (PAI-1), and type III and IV collagen significantly decreased (P < 0.01) in kidneys of diabetic KCa3.1-/- mice compared with diabetic wild-type mice. Similarly, TRAM34 reduced the expression of the inflammatory and fibrotic markers described above in diabetic eNOS-/- mice. Furthermore, blocking the KCa3.1 channel in both animal models led to a reduction of transforming growth factor-β1 (TGF-β1) and TGF-β1 type II receptor (TβRII) and phosphorylation of Smad2/3. Our results provide evidence that KCa3.1 mediates renal fibrosis in diabetic nephropathy through the TGF-β1/Smad signaling pathway. Blockade of KCa3.1 may be a novel target for therapeutic intervention in patients with diabetic nephropathy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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