A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the...

Area of Science:

• Nephrology
• Cell Biology
• Pathology

Background:

• The ICR-derived glomerulonephritis (ICGN) mouse model exhibits nephrotic syndrome due to a Tensin2 mutation.
• Tensin2 deficiency leads to decreased nephrin, podocytopathy, albuminuria, and chronic renal failure.
• The role of glomerular endothelial cells (ECs) in Tensin2-deficient nephropathy is not well understood.

Purpose of the Study:

• To investigate alterations in glomerular ECs in the Tensin2-deficient ICGN mouse model during chronic renal failure.
• To examine the expression of EC-specific markers (PECAM-1, VE-cadherin) and myofibroblast marker (α-SMA) in glomerular ECs.

Main Methods:

• Histological examination of glomerular ECs in nephrotic (nep/nep) and non-nephrotic (+/nep) ICGN mice.
• Immunohistochemical staining for PECAM-1, VE-cadherin, and α-SMA.

Main Results:

• Nephrotic mice showed reduced expression of PECAM-1 and VE-cadherin in glomerular areas compared to non-nephrotic mice.
• Some glomerular ECs in nephrotic mice stained positive for both PECAM-1 and α-SMA.
• These findings suggest endothelial-to-mesenchymal transition (EndoMT) in glomerular ECs during disease progression.

Conclusions:

• Glomerular ECs are reduced in Tensin2-deficient nephropathy.
• Endothelial-to-mesenchymal transition (EndoMT) contributes to glomerular endothelial cell loss in this model.
• This study provides the first evidence of EC alterations, including EndoMT, in Tensin2-deficient kidney disease.