C‐reactive protein exacerbates epithelial‐mesenchymal transition through Wnt/β‐catenin and ERK signaling in streptozocin‐induced diabetic nephropathy

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 epimelial‐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 epimelial‐mesenchymal transition through Wnt/β‐catenin and ERK signaling in streptozocin‐induced diabetic nephropathy. FASEB J. 33, 6551–6563 (2019). http://www.fasebj.org

C-Reactive Protein and Cancer—Diagnostic and Therapeutic Insights

“…CRP is also known to activate and regulate complement activity and bind immune complexes ( 119 ). Many reports also detail the interactions of CRP with endothelial cells ( 119 ), platelets ( 120 ), neutrophils ( 121 ), monocytes/macrophages ( 117 , 122 ), epithelial cells ( 123 ), and fibroblasts ( 124 ).…”

Reduction in Serum High-Sensitivity C-Reactive Protein Favors Kidney Outcomes in Patients with Impaired Fasting Glucose or Diabetes

“…Following upstream of the inflammatory response from CRP to IL-6 to IL-1, increasing the availability of novel opportunities [29]. In addition, a recent study demonstrated that hs-CRP could bind to FcγRII on apoptotic cells and exacerbate epithelialmesenchymal transition via the Wnt/β-catenin and ERK1/2 signal paths, which could promote the incidence of diabetic kidney disease [30]. However, the potential pathophysiological mechanisms could be complicated and require more research studies to ascertain a target for controlling inflammation in the process of the development and progression of kidney disease.…”

Effect modification of the association between plasma glucose and diabetic kidney disease by hypersensitive C-reactive protein in patients with diabetes mellitus

“…In one recent cohort study, Lili Liu and his colleagues followed 3924 individuals with impaired fasting glucose or diabetes for 5 years and revealed reduction in hs-CRP levels was associated with the decreased risk of DKD in these participants [23]. A recent animal study also showed that hs-CRP could bind to FcγRII on apoptotic cells and exacerbate epithelialmesenchymal transition via the Wnt/β-catenin and ERK1/2 signal paths, which could promote the development of diabetic kidney disease [24]. This present study enriched the knowledge on their relationship.…”