NDT Advance Access originally published online on October 12, 2005
Nephrology Dialysis Transplantation 2006 21(2):548-549; doi:10.1093/ndt/gfi194
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Tubular expression of connective tissue growth factor correlates with interstitial fibrosis in type 2 diabetic nephropathy
Email: iromichi{at}saitama-med.ac.jpSir,
Connective tissue growth factor (CTGF) is a secreted protein implicated in multiple cellular events, and has been focused on as a player in the development of renal diseases, especially diabetic nephropathy [1,2]. Although CTGF expression is localized in the podocytes in the normal kidney [3], and mesangial cells produce CTGF leading to glomerulosclerosis in human kidney diseases [4], the cellular source of CTGF in interstitial fibrosis is still controversial even in the experimental animals [5,6]. We demonstrated in in vitro experiments and animal studies that tubular epithelium is an important source of CTGF in the fibrosing kidney [1,3,6]. Thus, we tried to find out what kind of cells were positive for CTGF in the interstitium of human kidney with type 2 diabetes.
Twelve renal biopsy specimens of advanced type 2 diabetic nephropathy with interstitial fibrosis were collected and used for the determination of CTGF protein localization after obtaining informed consent. CTGF protein was detected by immunohistochemistry with anti-CTGF antibody, and interstitial fibrosis was visualized by Masson's trichrome stain. Methods and quantitative analysis of histopathological findings by using a computerized image analyser were reported previously [3,6]. The demographic and histopathological in detail data of the enrolled patients are tabulated in Table 1. CTGF protein was found not only in the glomerular cells, vascular endothelial cells and interstitial cells, but also in the epithelial cells of various tubular segments in the diabetic kidney of Case 12 (Figure 1A). Degrees of expansion of CTGF+ tubular epithelium were significantly correlated with the other parameters shown in Table 1 except for age and HbA1C level, and its correlation with degrees of interstitial fibrosis was the most prominent in the cases with advanced diabetic nephropathy collected in this study (Figure 1B). This significant expansion of the CTGF+ tubular area likely accounts for progressive extracellular matrix accumulation in the tubular basement membrane and the interstitium in the diabetic nephropathy via its autocrine and paracrine functions. Urine CTGF levels were found to be elevated in the patients with diabetic nephropathy [7], and we suppose that such CTGF is derived from tubular epithelial cells as well as glomerular cells. Some CTGF may be taken up by the tubular epithelial cells from the urine, and it acts as an intranuclear transcriptional factor [8]. In conclusion, the present finding suggests that tubular CTGF is of importance for tubulo-interstitial fibrogenesis in the type 2 diabetic nephropathy, and likely a target for anti-fibrosis therapy.
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Conflict of interest statement. None declared.
Department of Nephrology Saitama Medical School Saitama Japan
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