title: A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).
abstract: The ICR-derived glomerulonephritis (ICGN) mouse is a unique model of nephrotic syndrome, and albuminuria becomes evident in a neonatal stage, due to a genetic mutation of tensin2. We previously provided evidence that an apparent decrease in nephrin, caused by tensin2-deficiencient states, leads to podocytopathy, albuminuria and eventually, chronic renal failure. In general, glomerular endothelial cells (ECs) function as a barrier through tight attachment of glomerular basement membrane to podocytes, while decreased ECs can worsen renal failure. Nevertheless, it is still unknown whether glomerular ECs are altered under the tensin-2-deficient states during the manifestation of chronic renal failure. Herein, we examined the changes of glomerular ECs, with focus on the expression of PECAM-1 and VE-cadherin (EC-specific markers), or of α-SMA (myofibroblast marker) in this mouse model by histological methods. Compared with the non-nephrotic (+/nep) mice, the nephrotic (nep/nep) mice exhibited the reduced expression of PECAM-1, or of VE-cadherin, in glomerular area. Notably, some glomerular ECs showed the positive stainings for both PECAM-1 and α-SMA, suggesting endothelial-to-mesenchymal transition (EndoMT) during progression of glomerular sclerosis. This is the first report showing that a decrease in glomerular ECs, at least in part, via EndoMT is involved in tensin2-deficient pathological conditions.
authors: Department of Pathology, Faculty of Medicine, Kinki University , Osaka, Japan ; Division of Molecular Regenerative Medicine, Department of Biochemistry, Osaka University Graduate School of Medicine , Osaka, Japan.
authors: Takashi
authors: T
authors: Kato
authors: Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine , Osaka, Japan ; Division of Molecular Regenerative Medicine, Department of Biochemistry, Osaka University Graduate School of Medicine , Osaka, Japan.
authors: Shinya
authors: S
authors: Mizuno
authors: Department of Pathology, Faculty of Medicine, Kinki University , Osaka, Japan.
authors: Akihiko
authors: A
authors: Ito
keywords: ICGN mice; chronic kidney disease; endothelial mesenchymal transition; glomerular endothelial cells; glomerulosclerosis