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A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).

Kato T, Mizuno S, Ito A - Acta Histochem Cytochem (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical images of VE-cadherin at 5 and 20 weeks of age. (A) 5W of heterozygotes, (B) 5W of homozygotes, (C) 20W of heterozygotes, (D) 20W of homozygotes. (E) Quantification of VE-cadherin-positive cells per glomerulus. All data are expressed as mean ± SD (n=6). Statistical analysis: *p < 0.05, ***p < 0.001 as compared with age-matched heterozygous mice. Bars=20 μm.
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Figure 2: Immunohistochemical images of VE-cadherin at 5 and 20 weeks of age. (A) 5W of heterozygotes, (B) 5W of homozygotes, (C) 20W of heterozygotes, (D) 20W of homozygotes. (E) Quantification of VE-cadherin-positive cells per glomerulus. All data are expressed as mean ± SD (n=6). Statistical analysis: *p < 0.05, ***p < 0.001 as compared with age-matched heterozygous mice. Bars=20 μm.

Mentions: Several lines of evidence indicate that renal capillary loss is one of the most key events for accelerating CKD. We used VE-cadherin as a histological marker to detect glomerular ECs [31]. Indeed, we confirmed that this marker was localized along the capillary lumen (i.e., inside of synaptopodin-positive podocytic foot process) (not shown), and such a staining pattern was similar to the previous report [31]. In the non-nephrotic (+/nep) mice, the number of glomerular ECs (i.e., VE-cadherin-positive cells) remained unchanged between 5 and 20 weeks after birth (Fig. 2A, C). In contrast, there was a gradual decrease of the glomerular ECs in the nephrotic ICGN (nep/nep) mice (Fig. 2B, D). There was a significant difference in the number of glomerular ECs (5 and 20 weeks of age) between the normal and nephrotic groups (Fig. 2E).


A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).

Kato T, Mizuno S, Ito A - Acta Histochem Cytochem (2014)

Immunohistochemical images of VE-cadherin at 5 and 20 weeks of age. (A) 5W of heterozygotes, (B) 5W of homozygotes, (C) 20W of heterozygotes, (D) 20W of homozygotes. (E) Quantification of VE-cadherin-positive cells per glomerulus. All data are expressed as mean ± SD (n=6). Statistical analysis: *p < 0.05, ***p < 0.001 as compared with age-matched heterozygous mice. Bars=20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Immunohistochemical images of VE-cadherin at 5 and 20 weeks of age. (A) 5W of heterozygotes, (B) 5W of homozygotes, (C) 20W of heterozygotes, (D) 20W of homozygotes. (E) Quantification of VE-cadherin-positive cells per glomerulus. All data are expressed as mean ± SD (n=6). Statistical analysis: *p < 0.05, ***p < 0.001 as compared with age-matched heterozygous mice. Bars=20 μm.
Mentions: Several lines of evidence indicate that renal capillary loss is one of the most key events for accelerating CKD. We used VE-cadherin as a histological marker to detect glomerular ECs [31]. Indeed, we confirmed that this marker was localized along the capillary lumen (i.e., inside of synaptopodin-positive podocytic foot process) (not shown), and such a staining pattern was similar to the previous report [31]. In the non-nephrotic (+/nep) mice, the number of glomerular ECs (i.e., VE-cadherin-positive cells) remained unchanged between 5 and 20 weeks after birth (Fig. 2A, C). In contrast, there was a gradual decrease of the glomerular ECs in the nephrotic ICGN (nep/nep) mice (Fig. 2B, D). There was a significant difference in the number of glomerular ECs (5 and 20 weeks of age) between the normal and nephrotic groups (Fig. 2E).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus