Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment.

Chunming Jiang,Bo Jin,Miao Zhang,Biao Xu,Qiuyuan Shao,Rujun Gong

doi:10.1155/2015/867140

Abstract

Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFβ1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI.

Highlights

Acute kidney injury (AKI) is a severe and common disease found in clinical practice
We demonstrate that Tanshinone IIA treatment exerts beneficial effects on renal fibrosis of a mouse model of folic acid induced AKI
Our results showed that the accumulation of fibrocytes in the kidney was suppressed by Tanshinone IIA treatment at the early stage of AKI

Summary

Introduction

Acute kidney injury (AKI) is a severe and common disease found in clinical practice. Recent data demonstrated that AKI occurs in about 3.2–9.6% of hospital admissions with overall mortality around 20% [1, 2]. A growing body of evidence has shown a close connection between AKI and subsequent chronic kidney disease (CKD), which substantially increases the long-term morbidity and mortality of AKI [4, 5]. Enormous efforts have been dedicated to the understanding of the underlying pathophysiology of AKI; the exact mechanism contributing to AKI to CKD transition has not been fully elucidated. Recent evidence indicates that fibrocytes play an important role in promoting tissue fibrosis in various diseases including CKD [8,9,10,11]. It is well recognized that the migration of fibrocytes is mainly determined by chemoattractants due to their high expression of chemokine receptors and quick presentation

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Conclusion