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Hydrogen peroxide-inducible clone-5 regulates mesangial cell proliferation in proliferative glomerulonephritis in mice.

Jamba A, Kondo S, Urushihara M, Nagai T, Kim-Kaneyama JR, Miyazaki A, Kagami S - PLoS ONE (2015)

Bottom Line: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein.In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21.In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.

ABSTRACT
Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry for Ki-67 in Hic-5+/+ and Hic-5-/- glomerulonephritis (GN) mice.(a) On day 7, Hic-5+/+ Habu GN mice showed a greater number of Ki-67-positive glomerular cells. In addition, more Ki-67-positive cells were observed in the glomeruli of Hic-5-/- Habu GN mice. There were few Ki-67-positive cells in the glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. Original magnification x200, scale bar = 50 μm. (b) The number of Ki-67-positive cells was counted in 30 glomeruli per section and calculated. The data are shown as the means ± SD. *, P<0.01. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
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pone.0122773.g002: Immunohistochemistry for Ki-67 in Hic-5+/+ and Hic-5-/- glomerulonephritis (GN) mice.(a) On day 7, Hic-5+/+ Habu GN mice showed a greater number of Ki-67-positive glomerular cells. In addition, more Ki-67-positive cells were observed in the glomeruli of Hic-5-/- Habu GN mice. There were few Ki-67-positive cells in the glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. Original magnification x200, scale bar = 50 μm. (b) The number of Ki-67-positive cells was counted in 30 glomeruli per section and calculated. The data are shown as the means ± SD. *, P<0.01. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.

Mentions: Glomerular Ki-67 (a marker of proliferating cells)-positive cells were significantly increased in Hic-5+/+ GN mice on day 7. The glomeruli of Hic-5-/- GN mice contained more Ki-67-positive cells than those of Hic-5+/+ GN mice on day 7 (Fig 2). On day 0, the glomeruli of Hic-5+/+ and Hic-5-/- mice contained few Ki-67-positive cells.


Hydrogen peroxide-inducible clone-5 regulates mesangial cell proliferation in proliferative glomerulonephritis in mice.

Jamba A, Kondo S, Urushihara M, Nagai T, Kim-Kaneyama JR, Miyazaki A, Kagami S - PLoS ONE (2015)

Immunohistochemistry for Ki-67 in Hic-5+/+ and Hic-5-/- glomerulonephritis (GN) mice.(a) On day 7, Hic-5+/+ Habu GN mice showed a greater number of Ki-67-positive glomerular cells. In addition, more Ki-67-positive cells were observed in the glomeruli of Hic-5-/- Habu GN mice. There were few Ki-67-positive cells in the glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. Original magnification x200, scale bar = 50 μm. (b) The number of Ki-67-positive cells was counted in 30 glomeruli per section and calculated. The data are shown as the means ± SD. *, P<0.01. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4383376&req=5

pone.0122773.g002: Immunohistochemistry for Ki-67 in Hic-5+/+ and Hic-5-/- glomerulonephritis (GN) mice.(a) On day 7, Hic-5+/+ Habu GN mice showed a greater number of Ki-67-positive glomerular cells. In addition, more Ki-67-positive cells were observed in the glomeruli of Hic-5-/- Habu GN mice. There were few Ki-67-positive cells in the glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. Original magnification x200, scale bar = 50 μm. (b) The number of Ki-67-positive cells was counted in 30 glomeruli per section and calculated. The data are shown as the means ± SD. *, P<0.01. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
Mentions: Glomerular Ki-67 (a marker of proliferating cells)-positive cells were significantly increased in Hic-5+/+ GN mice on day 7. The glomeruli of Hic-5-/- GN mice contained more Ki-67-positive cells than those of Hic-5+/+ GN mice on day 7 (Fig 2). On day 0, the glomeruli of Hic-5+/+ and Hic-5-/- mice contained few Ki-67-positive cells.

Bottom Line: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein.In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21.In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.

ABSTRACT
Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis.

No MeSH data available.


Related in: MedlinePlus