کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8961825 | 1646520 | 2018 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential expression of cyclosporine A-Induced calcineurin isoform-specific matrix metalloproteinase 9 (MMP-9) in renal fibroblasts
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Long-term treatment with the potent immunosuppressive drug cyclosporine A (CsA) results in chronic nephrotoxicity. Its immunosuppressive properties are due to the inhibition of the calcium- and calmodulin-dependent phosphatase protein calcineurin A (CnA) which has three catalytic isoforms. Of those, the CnAα and β isoforms are ubiquitously expressed, particularly in the kidney. Additionally, chronic nephrotoxicity has been associated with an imbalance of extracellular matrix (ECM) synthesis and degradation resulting in an accumulation of ECM molecules. This study evaluates whether the expressions of matrix metalloproteinases (MMP-2 and MMP-9) induced by CsA are calcineurin isoform specific. Wild-type (WT), CnAα knockout (CnAαâ/â) and CnAβ knockout (CnAβâ/â) kidney fibroblast cell lines (an in vitro innovative tool that was previously created in our lab) were treated with CsA at 10â¯ng/ml for 48â¯h. ELISA analysis demonstrated that the CsA-induced secretion profile of MMP-9 was highest in CnAαâ/â cells and lowest in CnAβâ/â cells vs. WT cells. In contrast, CsA did not induce an increase in MMP-2 protein levels in WT, CnAαâ/â nor CnAβâ/â renal fibroblasts. These results indicate that MMP-9 secretion is CnA-isoform specific, i.e. the CnAβ isoform contributes to the CsA-induced upregulation of MMP-9 while the CnAα does not. As such, understanding the role of calcineurin A isoforms in the regulation of the homeostasis of ECM degradation in the kidney after long-term CsA treatment needs to be further investigated.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 503, Issue 4, 18 September 2018, Pages 2549-2554
Journal: Biochemical and Biophysical Research Communications - Volume 503, Issue 4, 18 September 2018, Pages 2549-2554
نویسندگان
Cynthia E. Francis, Yun Bai,