High glucose up-regulates microRNA-34a-5p to aggravate fibrosis by targeting SIRT1 in HK-2 cells

High glucose up-regulates microRNA-34a-5p to aggravate fibrosis by targeting SIRT1 in HK-2 cells Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells. We then demonstrated that overexpression of SIRT1 reduced, whereas small interfering RNA targeting SIRT1 enhanced the expressions of TGF-β1 and fibrosis-related genes including FN and COL1 in HK-2 cells. Furthermore, we identified that miR-34a-5p directly suppressed SIRT1 to increase the profibrogenic effects of TGFβ1 through targeting the 3'untranslated region of SIRT1. The functional correlation of miR-34a-5p induced SIRT1 decrease was supported by overexpression and inhibition of miR-34a-5p in HK-2 cells. All the results reveal that SIRT1 which is vital in the evolution of renal TIF in DN can be directly suppressed by miR-34a-5p, and suggest that miR-34a-5p is a new target for DN treatment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochemical and Biophysical Research Communications Elsevier

High glucose up-regulates microRNA-34a-5p to aggravate fibrosis by targeting SIRT1 in HK-2 cells

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Inc.
ISSN
0006-291x
D.O.I.
10.1016/j.bbrc.2017.12.048
Publisher site
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Abstract

Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells. We then demonstrated that overexpression of SIRT1 reduced, whereas small interfering RNA targeting SIRT1 enhanced the expressions of TGF-β1 and fibrosis-related genes including FN and COL1 in HK-2 cells. Furthermore, we identified that miR-34a-5p directly suppressed SIRT1 to increase the profibrogenic effects of TGFβ1 through targeting the 3'untranslated region of SIRT1. The functional correlation of miR-34a-5p induced SIRT1 decrease was supported by overexpression and inhibition of miR-34a-5p in HK-2 cells. All the results reveal that SIRT1 which is vital in the evolution of renal TIF in DN can be directly suppressed by miR-34a-5p, and suggest that miR-34a-5p is a new target for DN treatment.

Journal

Biochemical and Biophysical Research CommunicationsElsevier

Published: Mar 25, 2018

References

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