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, 33 (5), 6551-6563

C-reactive Protein Exacerbates Epithelial-Mesenchymal Transition Through Wnt/β-catenin and ERK Signaling in Streptozocin-Induced Diabetic Nephropathy

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C-reactive Protein Exacerbates Epithelial-Mesenchymal Transition Through Wnt/β-catenin and ERK Signaling in Streptozocin-Induced Diabetic Nephropathy

Lin Zhang et al. FASEB J.

Abstract

Previous studies have reported the pathogenic role of C-reactive protein (CRP) during diabetic kidney disease (DKD) in human CRP transgenic and Crp-/- mice. However, because humans and mice have inverse acute phase expression patterns of CRP and serum amyloid P component, this could lead to the inaccurate evaluation of CRP function with the above-mentioned CRP transgenic mouse. But different from mice, rats have the same acute phase protein expression pattern as human, which might avoid this problem and be a better choice for CRP function studies. To dispel this doubt and accurately define the role of CRP during diabetic nephropathy, we created the first Crp-/- rat model, which we treated with streptozocin to induce DKD for in vivo studies. Moreover, an established cell line (human kidney 2) was used to further investigate the pathologic mechanisms of CRP. We found that CRP promotes epithelial-mesenchymal transition (EMT) through Wnt/β-catenin and ERK1/2 signaling, which are dependent on CRP binding to FcγRII on apoptotic cells. By promoting EMT, CRP was demonstrated to accelerate the development of DKD. We thus present convincing evidence demonstrating CRP as a therapeutic target for DKD treatment.-Zhang, L., Shen, Z.-Y., Wang, K., Li, W., Shi, J.-M., Osoro, E. K., Ullah, N., Zhou, Y., Ji, S.-R. C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/β-catenin and ERK signaling in streptozocin-induced diabetic nephropathy.

Keywords: apoptotic cells; cell remodeling; diabetic kidney disease; mesenchymal fibrosis.

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