Next Article in Journal
Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities
Next Article in Special Issue
Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study
Previous Article in Journal
Biodegradable Polymers Influence the Effect of Atorvastatin on Human Coronary Artery Cells
Previous Article in Special Issue
Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(2), 146; doi:10.3390/ijms17020146

Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts

Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Author to whom correspondence should be addressed.
Academic Editor: Alan Parrish
Received: 27 November 2015 / Revised: 13 January 2016 / Accepted: 20 January 2016 / Published: 22 January 2016
(This article belongs to the Special Issue Advances in Chronic Kidney Disease)
View Full-Text   |   Download PDF [4992 KB, uploaded 25 January 2016]   |  


Renal fibrosis is the final common pathway of chronic kidney disease (CKD), and no effective medication is available clinically for managing its progression. Metformin was initially developed as an anti-diabetic drug and recently gained attention for its potential in the treatment of other diseases. In this study, we investigated its effects on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) in vivo and in angiotensin II (Ang II)–treated renal fibroblast NRK-49F cells in vitro. Our data showed that UUO induced renal fibrosis and combined with the activation of ERK signaling, the upregulation of fibronectin, collagen I, and transforming growth factor-β (TGF-β). The administration of metformin inhibited the activation of ERK signaling and attenuated the production of extracellular matrix (ECM) proteins and collagen deposition in the obstructed kidneys. In cultured renal fibroblasts, Ang II increased the expression of fibronectin and collagen I and also activated ERK signaling and TGF-β in a time-dependent manner. Pretreatment of the cells with metformin blocked Ang II–induced ERK signaling activation and ECM overproduction. Our results show that metformin prevents renal fibrosis, possibly through the inhibition of ERK signaling, and may be a novel strategy for the treatment of renal fibrosis. View Full-Text
Keywords: metformin; renal fibrosis; ERK; angiotensin II; transforming growth factor-β metformin; renal fibrosis; ERK; angiotensin II; transforming growth factor-β

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Shen, Y.; Miao, N.; Xu, J.; Gan, X.; Xu, D.; Zhou, L.; Xue, H.; Zhang, W.; Lu, L. Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts. Int. J. Mol. Sci. 2016, 17, 146.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top