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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

Semi-quantitative assessment of the glomerular expression of PDGF-B chain, PDGF receptor, TGF-β1, and TGF-β receptor.The glomerular expression of PDGF-B chain (a), PDGF receptor β subunit (PDGF-R-β) (b), TGF-β1 (c), and TGF-β receptor type II (TGF-β-R) (d) in Hic-5+/+ and Hic-5-/- glomerulonephritis mice was determined as the positively immunoreactive fraction in the glomerular area based on the examination of 30 equatorially sectioned glomeruli for each section, and statistically analyzed. The data are shown as the means ± SD. *, P<0.01. N.S., not significant. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
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pone.0122773.g006: Semi-quantitative assessment of the glomerular expression of PDGF-B chain, PDGF receptor, TGF-β1, and TGF-β receptor.The glomerular expression of PDGF-B chain (a), PDGF receptor β subunit (PDGF-R-β) (b), TGF-β1 (c), and TGF-β receptor type II (TGF-β-R) (d) in Hic-5+/+ and Hic-5-/- glomerulonephritis mice was determined as the positively immunoreactive fraction in the glomerular area based on the examination of 30 equatorially sectioned glomeruli for each section, and statistically analyzed. The data are shown as the means ± SD. *, P<0.01. N.S., not significant. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.

Mentions: Since the increased MC proliferation and ECM accumulation in diseased glomeruli are affected by growth factors, we investigated the glomerular expression of PDGF-B chain and TGF-β1, and their receptors, against PDGF and TGF-β. The expression of both PDGF-B chain and TGF-β1 was weak in glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. On day 7, the expression was enhanced to a similar degree in glomeruli of Hic-5+/+ and Hic-5-/- GN mice. In addition, the expression of receptors against PDGF and TGF-β was similar to the expression of PDGF-B chain and TGF-β1 (Fig 5). Assessment by analyzing positively immunoreactive glomerular area showed that there were no significant differences between Hic-5+/+ and Hic-5-/- GN mice on days 0 and 7, respectively. These results suggested that Hic-5 did not affect the glomerular expression of PDGF-B chain, TGF-β1, or their receptors before or after glomerular injury (Fig 6).


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)

Semi-quantitative assessment of the glomerular expression of PDGF-B chain, PDGF receptor, TGF-β1, and TGF-β receptor.The glomerular expression of PDGF-B chain (a), PDGF receptor β subunit (PDGF-R-β) (b), TGF-β1 (c), and TGF-β receptor type II (TGF-β-R) (d) in Hic-5+/+ and Hic-5-/- glomerulonephritis mice was determined as the positively immunoreactive fraction in the glomerular area based on the examination of 30 equatorially sectioned glomeruli for each section, and statistically analyzed. The data are shown as the means ± SD. *, P<0.01. N.S., not significant. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122773.g006: Semi-quantitative assessment of the glomerular expression of PDGF-B chain, PDGF receptor, TGF-β1, and TGF-β receptor.The glomerular expression of PDGF-B chain (a), PDGF receptor β subunit (PDGF-R-β) (b), TGF-β1 (c), and TGF-β receptor type II (TGF-β-R) (d) in Hic-5+/+ and Hic-5-/- glomerulonephritis mice was determined as the positively immunoreactive fraction in the glomerular area based on the examination of 30 equatorially sectioned glomeruli for each section, and statistically analyzed. The data are shown as the means ± SD. *, P<0.01. N.S., not significant. There was no significant difference between Hic-5+/+ day 0 and Hic-5-/- day 0.
Mentions: Since the increased MC proliferation and ECM accumulation in diseased glomeruli are affected by growth factors, we investigated the glomerular expression of PDGF-B chain and TGF-β1, and their receptors, against PDGF and TGF-β. The expression of both PDGF-B chain and TGF-β1 was weak in glomeruli of Hic-5+/+ and Hic-5-/- mice on day 0. On day 7, the expression was enhanced to a similar degree in glomeruli of Hic-5+/+ and Hic-5-/- GN mice. In addition, the expression of receptors against PDGF and TGF-β was similar to the expression of PDGF-B chain and TGF-β1 (Fig 5). Assessment by analyzing positively immunoreactive glomerular area showed that there were no significant differences between Hic-5+/+ and Hic-5-/- GN mice on days 0 and 7, respectively. These results suggested that Hic-5 did not affect the glomerular expression of PDGF-B chain, TGF-β1, or their receptors before or after glomerular injury (Fig 6).

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