博士生周蒙文章被Kideny International (IF:8.52)接收-山东大学基础医学院药理学系

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博士生周蒙文章被Kideny International (IF:8.52)接收

作者：来源：发布时间：2014年10月19日 04:42 浏览次数：

Progranulin protects against renal ischemia/reperfusion injury in mice

Meng Zhou^1#, Wei Tang^2#, Yi Fu¹, Xiaoying Xu², Ziying Wang¹, Yi Lu³, Feng Liu³, Xinying Yang⁴, Xinbing Wei¹, Yan Zhang¹, Juan Liu², Xue Geng¹, Chun Zhang⁵, Qiang Wan⁶, Ningjun Li⁷, and Fan Yi^1,8*

¹Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China

²Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, 250012, China

³Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, 250012, China

⁴Institute of Pharmaceutical Analysis,School of Pharmacy, Shandong University, Jinan, 250012, China

⁵Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

⁶Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China

⁷Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA

⁸Institute of Nephrology, Shandong University, Jinan, 250012, China

^#Co-first authors, equally contributes to this work.

Running title: PGRN and ischemic renal injury

Words: 3129

*Send Correspondence and Reprint Requests to:

Fan Yi, Ph.D

Professor

Department of Pharmacology

Shandong University School of Medicine

44#, Wenhua Xi Road,

Jinan, Shandong, 250012, P.R. China

Phone: 86-0531-88382616

Fax: 86-0531-88382616

E-mail: fanyi@sdu.edu.cn

Abstract

Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encourages us to further elucidate the role of PGRN in acute kidney injury (AKI). In this study, we found that the levels of PGRN were significantly reduced in the kidney from a mouse model of renal ischemia/reperfusion injury (IRI). We further observed that PGRN deficient (Grn^-/-) mice significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, increased tubular epithelial cell apoptosis, and tubulointerstitial neutrophil and macrophage infiltration versus wild type (WT) mice. In vitro, we demonstrated that recombinant PGRN (rPGRN) attenuated hypoxia-induced inflammatory actions and apoptosis in proximal tubule epithelial cells, which was associated with, at least in part, nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated immune response. Importantly, both WT and Grn^-/-mice pretreated with or delayed administration of rPGRN protected against or promoted recovery from renal IRI. Similar renal protective effects were also observed in cisplatin-induced AKI. Collectively, these findings provide new evidence for a better understanding of the biological activities of PGRN in the kidney and suggest that PGRN may be an innovative therapeutic strategy for treating patients with AKI.

Key words:

progranulin; acute kidney injury; pattern-recognition receptors; hypoxia; inflammation

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