Tubular CD146 Expression in Nephropathies Is Related to Chronic Renal Failure

Abstract

Background: CD146, a member of the immunoglobulin superfamily, is mainly expressed at the endothelial junction. The soluble form of CD146 is increased in the serum of patients with chronic renal failure. The aim of the study was to investigate CD146 expression on biopsies of normal kidney and nephropathies. Methods: We did an immunohistochemical analysis of 10 normal renal tissues and 126 patients with nephropathies. Results: The mean age of the patients was 47.5 ± 18 years with 65% of men. At the time of the biopsy, 73 patients (57.9%) had a renal failure and the mean proteinuria was 3.3 ± 2.9 g/24 h. Inflammatory syndrome was present in 60 (47.6%) patients. Fibrous interstitial changes from minimal lesions to diffuse lesions were seen in 105 (83.3%) biopsies; the mean glomerulosclerosis index was 16.9 ± 19.7%. Normal kidneys showed CD146 staining on endothelial cells, smooth muscle cells, and mesangium. Normal tubular cells were not stained. If endocapillary proliferation was present, the mesangial CD146 expression was higher. This mesangial expression correlated with proteinuria (p = 0.007) and not with renal failure (p = 0.07). A de novo expression on tubular cells was found in 53 patients (42%) and this expression correlated with age (p < 0.001), male sex (p = 0.04), glomerulosclerosis (p < 0.001), interstitial fibrosis (p < 0.001), and renal failure (p < 0.001). Conclusion: Renal CD146 expression is of interest for determining the pathogenesis of mesangial alterations during glomerular injuries and of tubular phenotypic changes during chronic renal failure.

CD146 + cells are essential for kidney vasculature development

“…31 The vascular ECs of the normal adult human kidney express CD146, but increases in vascular expression and de novo expression in tubular cells can occur in nephropathies. 32 Moreover, increased concentrations of soluble CD146 are observed in patients with chronic renal failure, correlating with EC injury markers. 33 A mouse model of renal ischemia/ reperfusion injury has revealed that cell therapy with human bone marrow-derived stem cells increases survival via regeneration of the peritubular vasculature.…”

Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

“…In addition to physiological angiogenesis, α6β1 integrin and MCAM interaction with α4-laminins may contribute to tissue regeneration as reported for nerves and liver . Notably, MCAM is expressed by mesenchymal stem cells and glomerular mesangial cells, and the latter cells use endogenous laminin-421 to migrate (Daniel et al, 2005;Berfield et al, 2006;Wang and Yan, 2013). The molecular interactions may also mediate leukocyte trans-endothelial migration during inflammation (Wondimu et al, 2004;Bardin et al, 2009;Flanagan et al, 2012).…”

“…Melanoma cell adhesion molecule (MCAM), also known as CD146, MUC18, MelCAM, A32 antigen, METCAM, and gicerin, is a cell-surface molecule of the Ig superfamily with expression in normal tissues restricted to vascular endothelial cells, smooth muscle cells, glomerular mesangial cells, Schwann cells, intermediate trophoblasts, mesenchymal stem cells, some leukocytes, and a few other cell types (Shih et al, 1998;Daniel et al, 2005;Wang and Yan, 2013). Originally identified as a tumor marker for melanoma (Lehmann et al, 1987), MCAM is also detected in prostate cancer, osteosarcoma, and other tumors, and its expression is closely related to tumor invasion and metastasis and poor survival .…”

MicroRNA 329 Suppresses Angiogenesis by Targeting CD146

“…The importance of CD146 in physiological angiogenesis was illustrated by an earlier study of its regulation of intersegmental vessel development in zebrafish (9). During pathological angiogenesis, CD146 expression is upregulated in the endothelial cells involved in angiogenic diseases, including tumors (8), chronic renal failure (10), inflammatory bowel disease (11), and rheumatoid arthritis (12). The expression level of endothelial CD146 directly correlates with endothelial cell proliferation, migration, and tube formation (13,14).…”