Podocyte expression of the CDK-inhibitor p57 during development and disease

K. Hiromura, L. A. Haseley, P. Zhang, Toshiaki Monkawa, R. Durvasula, A. T. Petermann, C. E. Alpers, P. Mundel, S. J. Shankland

研究成果: Article

74 引用 (Scopus)

抄録

Background. The mature podocyte is a terminally differentiated cell with a limited proliferative capacity. The precise cell cycle proteins necessary for establishing podocyte quiescence during development or permitting podocyte cell cycle re-entry in disease states have not been fully defined. Accordingly, we studied the role of the cyclin dependent kinase (CDK)-inhibitor p57Kip2 (p57) in modulating these processes. Methods. The expression of p57 protein in relation to markers of DNA synthesis was examined in developing mouse kidneys, and in the passive Heymann nephritis (PHN) and anti-glomerular antibody models of glomerular disease by immunohistochemistry. The role of p57 in glomerulogenesis was explored by examining renal tissue from embryonic p57-/- mice, and the expression of p21, p27 and p57 protein and mRNA was examined in podocytes in vitro. Results. The de novo expression of p57 during glomerulogenesis coincides with the cessation of podocyte proliferation, and the establishment of a mature phenotype, and p57 is expressed exclusively in podocytes in mature glomeruli. However, p57 knockout mice have normal glomerular podocyte development. In addition, mRNA but not protein levels of p57 increased upon differentiation of podocytes in vitro. There was a marked decrease in p57 expression in both animal models of podocyte injury. This was diffuse in PHN, whereas in the murine model, loss of expression of p57 occurred predominantly in proliferating podocytes, expressing proliferating cell nuclear antigen (PCNA). Conclusion. Despite the de novo expression of p57 protein coinciding with the cessation of primitive podocyte proliferation during glomerulogenesis, embryonic p57-/- mice glomeruli were histologically normal. Cultured podocytes did not require changes in p57 protein levels to undergo differentiation. These data suggest that p57 alone is not required for podocyte differentiation, and that other cell cycle regulators may play a role. Furthermore, although injury to mature podocytes in experimental glomerular disease is associated with a decrease in p57, the levels of all three members of the Cip/Kip family of CDK inhibitors appear to determine the capability of podocytes to proliferate.

元の言語English
ページ(範囲)2235-2246
ページ数12
ジャーナルKidney International
60
発行部数6
DOI
出版物ステータスPublished - 2001
外部発表Yes

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Podocytes
Cyclin-Dependent Kinases
Cyclin-Dependent Kinase Inhibitor p57
Membranous Glomerulonephritis
Cell Cycle
Kidney
Cell Cycle Proteins
Messenger RNA
Wounds and Injuries
Proliferating Cell Nuclear Antigen
Genetic Markers
Knockout Mice

ASJC Scopus subject areas

  • Nephrology

これを引用

Hiromura, K., Haseley, L. A., Zhang, P., Monkawa, T., Durvasula, R., Petermann, A. T., ... Shankland, S. J. (2001). Podocyte expression of the CDK-inhibitor p57 during development and disease. Kidney International, 60(6), 2235-2246. https://doi.org/10.1046/j.1523-1755.2001.00057.x

Podocyte expression of the CDK-inhibitor p57 during development and disease. / Hiromura, K.; Haseley, L. A.; Zhang, P.; Monkawa, Toshiaki; Durvasula, R.; Petermann, A. T.; Alpers, C. E.; Mundel, P.; Shankland, S. J.

:: Kidney International, 巻 60, 番号 6, 2001, p. 2235-2246.

研究成果: Article

Hiromura, K, Haseley, LA, Zhang, P, Monkawa, T, Durvasula, R, Petermann, AT, Alpers, CE, Mundel, P & Shankland, SJ 2001, 'Podocyte expression of the CDK-inhibitor p57 during development and disease', Kidney International, 巻. 60, 番号 6, pp. 2235-2246. https://doi.org/10.1046/j.1523-1755.2001.00057.x
Hiromura, K. ; Haseley, L. A. ; Zhang, P. ; Monkawa, Toshiaki ; Durvasula, R. ; Petermann, A. T. ; Alpers, C. E. ; Mundel, P. ; Shankland, S. J. / Podocyte expression of the CDK-inhibitor p57 during development and disease. :: Kidney International. 2001 ; 巻 60, 番号 6. pp. 2235-2246.
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abstract = "Background. The mature podocyte is a terminally differentiated cell with a limited proliferative capacity. The precise cell cycle proteins necessary for establishing podocyte quiescence during development or permitting podocyte cell cycle re-entry in disease states have not been fully defined. Accordingly, we studied the role of the cyclin dependent kinase (CDK)-inhibitor p57Kip2 (p57) in modulating these processes. Methods. The expression of p57 protein in relation to markers of DNA synthesis was examined in developing mouse kidneys, and in the passive Heymann nephritis (PHN) and anti-glomerular antibody models of glomerular disease by immunohistochemistry. The role of p57 in glomerulogenesis was explored by examining renal tissue from embryonic p57-/- mice, and the expression of p21, p27 and p57 protein and mRNA was examined in podocytes in vitro. Results. The de novo expression of p57 during glomerulogenesis coincides with the cessation of podocyte proliferation, and the establishment of a mature phenotype, and p57 is expressed exclusively in podocytes in mature glomeruli. However, p57 knockout mice have normal glomerular podocyte development. In addition, mRNA but not protein levels of p57 increased upon differentiation of podocytes in vitro. There was a marked decrease in p57 expression in both animal models of podocyte injury. This was diffuse in PHN, whereas in the murine model, loss of expression of p57 occurred predominantly in proliferating podocytes, expressing proliferating cell nuclear antigen (PCNA). Conclusion. Despite the de novo expression of p57 protein coinciding with the cessation of primitive podocyte proliferation during glomerulogenesis, embryonic p57-/- mice glomeruli were histologically normal. Cultured podocytes did not require changes in p57 protein levels to undergo differentiation. These data suggest that p57 alone is not required for podocyte differentiation, and that other cell cycle regulators may play a role. Furthermore, although injury to mature podocytes in experimental glomerular disease is associated with a decrease in p57, the levels of all three members of the Cip/Kip family of CDK inhibitors appear to determine the capability of podocytes to proliferate.",
keywords = "Cell cycle, Cyclin dependent kinase, Glomerular epithelial cell, Kidney, P57, Podocyte, Renal failure",
author = "K. Hiromura and Haseley, {L. A.} and P. Zhang and Toshiaki Monkawa and R. Durvasula and Petermann, {A. T.} and Alpers, {C. E.} and P. Mundel and Shankland, {S. J.}",
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T1 - Podocyte expression of the CDK-inhibitor p57 during development and disease

AU - Hiromura, K.

AU - Haseley, L. A.

AU - Zhang, P.

AU - Monkawa, Toshiaki

AU - Durvasula, R.

AU - Petermann, A. T.

AU - Alpers, C. E.

AU - Mundel, P.

AU - Shankland, S. J.

PY - 2001

Y1 - 2001

N2 - Background. The mature podocyte is a terminally differentiated cell with a limited proliferative capacity. The precise cell cycle proteins necessary for establishing podocyte quiescence during development or permitting podocyte cell cycle re-entry in disease states have not been fully defined. Accordingly, we studied the role of the cyclin dependent kinase (CDK)-inhibitor p57Kip2 (p57) in modulating these processes. Methods. The expression of p57 protein in relation to markers of DNA synthesis was examined in developing mouse kidneys, and in the passive Heymann nephritis (PHN) and anti-glomerular antibody models of glomerular disease by immunohistochemistry. The role of p57 in glomerulogenesis was explored by examining renal tissue from embryonic p57-/- mice, and the expression of p21, p27 and p57 protein and mRNA was examined in podocytes in vitro. Results. The de novo expression of p57 during glomerulogenesis coincides with the cessation of podocyte proliferation, and the establishment of a mature phenotype, and p57 is expressed exclusively in podocytes in mature glomeruli. However, p57 knockout mice have normal glomerular podocyte development. In addition, mRNA but not protein levels of p57 increased upon differentiation of podocytes in vitro. There was a marked decrease in p57 expression in both animal models of podocyte injury. This was diffuse in PHN, whereas in the murine model, loss of expression of p57 occurred predominantly in proliferating podocytes, expressing proliferating cell nuclear antigen (PCNA). Conclusion. Despite the de novo expression of p57 protein coinciding with the cessation of primitive podocyte proliferation during glomerulogenesis, embryonic p57-/- mice glomeruli were histologically normal. Cultured podocytes did not require changes in p57 protein levels to undergo differentiation. These data suggest that p57 alone is not required for podocyte differentiation, and that other cell cycle regulators may play a role. Furthermore, although injury to mature podocytes in experimental glomerular disease is associated with a decrease in p57, the levels of all three members of the Cip/Kip family of CDK inhibitors appear to determine the capability of podocytes to proliferate.

AB - Background. The mature podocyte is a terminally differentiated cell with a limited proliferative capacity. The precise cell cycle proteins necessary for establishing podocyte quiescence during development or permitting podocyte cell cycle re-entry in disease states have not been fully defined. Accordingly, we studied the role of the cyclin dependent kinase (CDK)-inhibitor p57Kip2 (p57) in modulating these processes. Methods. The expression of p57 protein in relation to markers of DNA synthesis was examined in developing mouse kidneys, and in the passive Heymann nephritis (PHN) and anti-glomerular antibody models of glomerular disease by immunohistochemistry. The role of p57 in glomerulogenesis was explored by examining renal tissue from embryonic p57-/- mice, and the expression of p21, p27 and p57 protein and mRNA was examined in podocytes in vitro. Results. The de novo expression of p57 during glomerulogenesis coincides with the cessation of podocyte proliferation, and the establishment of a mature phenotype, and p57 is expressed exclusively in podocytes in mature glomeruli. However, p57 knockout mice have normal glomerular podocyte development. In addition, mRNA but not protein levels of p57 increased upon differentiation of podocytes in vitro. There was a marked decrease in p57 expression in both animal models of podocyte injury. This was diffuse in PHN, whereas in the murine model, loss of expression of p57 occurred predominantly in proliferating podocytes, expressing proliferating cell nuclear antigen (PCNA). Conclusion. Despite the de novo expression of p57 protein coinciding with the cessation of primitive podocyte proliferation during glomerulogenesis, embryonic p57-/- mice glomeruli were histologically normal. Cultured podocytes did not require changes in p57 protein levels to undergo differentiation. These data suggest that p57 alone is not required for podocyte differentiation, and that other cell cycle regulators may play a role. Furthermore, although injury to mature podocytes in experimental glomerular disease is associated with a decrease in p57, the levels of all three members of the Cip/Kip family of CDK inhibitors appear to determine the capability of podocytes to proliferate.

KW - Cell cycle

KW - Cyclin dependent kinase

KW - Glomerular epithelial cell

KW - Kidney

KW - P57

KW - Podocyte

KW - Renal failure

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