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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00224

CXCL6 promotes renal interstitial fibrosis in diabetic nephropathy by activating JAK/STAT3 signaling pathway

Meng-Yao Sun1, Su-Juan Wang1, Yu-Li Shen1, Jian-Rao Lu1,  Xin Hui Tian2, Khalid Rahma3, Li-Jun Zhang1,  Hua Nian4 and  Hong Zhang2*
  • 1Seventh People's Hospital of Shanghai, China
  • 2Shanghai University of Traditional Chinese Medicine, China
  • 3Liverpool John Moores University, United Kingdom
  • 4Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China

In this study the role of CXCL6 in diabetic nephropathy (DN) was investigated. It was found to be overexpression in DN patients and DN rat model. And the expression of fibrosis-related cytokines was consistent with the expression of CXCL6. High glucose significantly increased the proliferation of rat renal fibroblasts NRK-49F cell and the expression of CXCL6. Knockdown of CXCL6 ameliorated the pro-proliferation effect of high glucose and decreased the expression of fibrosis-related cytokines, while CXCL6 overexpression exhibited the opposite phenomenon. Gene set enrichment analysis, Western blot and ELISA showed that Janus kinase-signal transducer and activator of transcription (JAK-STAT) and CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION signaling pathways were correlative with CXCL6. This data indicates that CXCL6 may promote fibrosis-related factors to accelerate the development of diabetic nephropathy renal interstitial fibrosis by activating JAK/STAT3 signaling pathway. CXCL6 is promising to be a potential novel therapeutic target and candidate biomarker for JAK/STAT3 signaling for the treatment of DN.

Keywords: CXCL6, Kidney, Diabetics, Fibrosis, Pathway

Received: 25 Sep 2018; Accepted: 22 Feb 2019.

Edited by:

Matthew Griffin, National University of Ireland Galway, Ireland

Reviewed by:

Peter J. Nelson, Ludwig Maximilian University of Munich, Germany
Ana Belen Sanz, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Spain  

Copyright: © 2019 Sun, Wang, Shen, Lu, Tian, Rahma, Zhang, Nian and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Hong Zhang, Shanghai University of Traditional Chinese Medicine, Shanghai, China,