Journal of Cell Communication and Signaling

, Volume 5, Issue 3, pp 193–200 | Cite as

CCN-2 is up-regulated by and mediates effects of matrix bound advanced glycated end-products in human renal mesangial cells

  • Xiaoyu Wang
  • Susan V. McLennan
  • Stephen M. TwiggEmail author
Research Article


CCN-2, also known as connective tissue growth factor (CCN-2/CTGF) is a cysteine rich, extracellular matrix protein that acts as a pro-fibrotic cytokine in tissues in many diseases, including in diabetic nephropathy. We have published that soluble advanced glycation end products (AGEs), that are present in increased amounts in diabetes, induce CCN-2. However in vivo AGEs are known to be heavily tissue bound and whether matrix bound AGEs regulate CCN-2 has not been investigated. In this study we determined in human renal mesangial cells if CCN-2 is induced by matrix associated AGEs and if CCN-2 may then secondarily mediate effects of matrix AGEs on extracellular matrix expansion. Data generated show that CCN-2 mRNA and protein expression are induced by matrix bound AGEs, and in contrast, this was not the case for TGF-β1 mRNA regulation. Using CCN-2 adenoviral anti-sense it was found that CCN-2 mediated the up-regulation of fibronectin and the tissue inhibitor of matrix metalloproteinase, TIMP-1, that was caused by matrix bound AGEs. In conclusion, CCN-2 is induced by non-enzymatically glycated matrix and it mediates downstream fibronectin and TIMP-1 increases, thus through this mechanism potentially contributing to ECM accumulation in the renal glomerulus in diabetes.


CCN-2 Diabetic nephropathy Advanced glycation Matrix CTGF 



This study was supported by Project Grant #402559 from the National Health and Medical Research Council (NHMRC) of Australia and by the Endocrinology and Diabetes Research Foundation, The University of Sydney.


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Copyright information

© The International CCN Society 2011

Authors and Affiliations

  • Xiaoyu Wang
    • 1
  • Susan V. McLennan
    • 1
    • 2
  • Stephen M. Twigg
    • 1
    • 2
    Email author
  1. 1.Sydney Medical SchoolThe University of SydneySydneyAustralia
  2. 2.Department of EndocrinologyRoyal Prince Alfred HospitalSydneyAustralia

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