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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

Histological assessment of glomerular lesions in experimental glomerulonephritis (GN).(a) Periodic acid-Schiff staining in Habu venom-induced Hic-5+/+ and Hic-5-/- GN mice. On day 7, Hic-5+/+ GN Habu mice exhibited glomerular cell proliferation. Hic-5-/- Habu GN mice showed severe mesangial cell proliferation and intensive glomerular matrix expansion compared to Hic-5+/+ Habu GN mice. Original magnification x200, scale bar = 50 μm. (b) The number of glomerular 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. (c) A matrix score was assessed 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.g001: Histological assessment of glomerular lesions in experimental glomerulonephritis (GN).(a) Periodic acid-Schiff staining in Habu venom-induced Hic-5+/+ and Hic-5-/- GN mice. On day 7, Hic-5+/+ GN Habu mice exhibited glomerular cell proliferation. Hic-5-/- Habu GN mice showed severe mesangial cell proliferation and intensive glomerular matrix expansion compared to Hic-5+/+ Habu GN mice. Original magnification x200, scale bar = 50 μm. (b) The number of glomerular 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. (c) A matrix score was assessed 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: On day 7, Hic-5+/+ GN mice exhibited glomerular cell proliferation, and Hic-5-/- GN mice showed more severe glomerular cell proliferation and matrix expansion (Fig 1A). The glomerular cell number and matrix score in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7 (Fig 1 B and 1 C). Thereafter, glomerular cell proliferation similarly recovered around 4 weeks in both Hic-5+/+ and Hic-5-/- mice.


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)

Histological assessment of glomerular lesions in experimental glomerulonephritis (GN).(a) Periodic acid-Schiff staining in Habu venom-induced Hic-5+/+ and Hic-5-/- GN mice. On day 7, Hic-5+/+ GN Habu mice exhibited glomerular cell proliferation. Hic-5-/- Habu GN mice showed severe mesangial cell proliferation and intensive glomerular matrix expansion compared to Hic-5+/+ Habu GN mice. Original magnification x200, scale bar = 50 μm. (b) The number of glomerular 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. (c) A matrix score was assessed 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.g001: Histological assessment of glomerular lesions in experimental glomerulonephritis (GN).(a) Periodic acid-Schiff staining in Habu venom-induced Hic-5+/+ and Hic-5-/- GN mice. On day 7, Hic-5+/+ GN Habu mice exhibited glomerular cell proliferation. Hic-5-/- Habu GN mice showed severe mesangial cell proliferation and intensive glomerular matrix expansion compared to Hic-5+/+ Habu GN mice. Original magnification x200, scale bar = 50 μm. (b) The number of glomerular 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. (c) A matrix score was assessed 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: On day 7, Hic-5+/+ GN mice exhibited glomerular cell proliferation, and Hic-5-/- GN mice showed more severe glomerular cell proliferation and matrix expansion (Fig 1A). The glomerular cell number and matrix score in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7 (Fig 1 B and 1 C). Thereafter, glomerular cell proliferation similarly recovered around 4 weeks in both Hic-5+/+ and Hic-5-/- mice.

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