Skip to main content
Top
Published in: Clinical and Experimental Nephrology 2/2016

Open Access 01-04-2016 | Original Article

Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis

Authors: Yang Lu, Jun Wen, DaPeng Chen, LingLing Wu, QingGang Li, Yuansheng Xie, Di Wu, Xiaoluan Liu, XiangMei Chen

Published in: Clinical and Experimental Nephrology | Issue 2/2016

Login to get access

Abstract

Background

Mesangial cell (MC) proliferation and apoptosis are the main pathological changes observed in mesangial proliferative nephritis. In this study, we explored the role of cyclins and p53 in modulating MC proliferation and apoptosis in a mouse model of Habu nephritis.

Methods

The Habu nephritis group was prepared by injection of Habu toxin. Mesangiolysis and mesangial expansion were determined by periodic acid-Schiff (PAS) reagent staining. Immunohistochemical analysis of PCNA and KI67, and TUNEL staining were used to detect cell proliferation and apoptosis, respectively. Expression levels of cyclins and p53 were examined by Western blotting.

Results

PAS staining showed that mesangial dissolution appeared on days 1 and 3, and mesangial proliferation with extracellular matrix accumulation was apparent by days 7 and 14. Both PCNA and KI67 immunohistochemical analysis showed that MC proliferation began on day 3, peaked on day 3 and 7, and recovered by day 14. TUNEL staining results showed that MC apoptosis began to increase on day 1, continued to rise on day 7, and peaked on day 14. Western blot analysis showed that cyclin D1 was upregulated on day 1, cyclins A2 and E were upregulated on days 3 and 7, and p53 was upregulated on days 3, 7 and 14. There was no change in the expression levels of Bax or p21.

Conclusion

We explored the tendency for MC proliferation and apoptosis during the process of Habu nephritis and found that cyclins and p53 may modulate the disease pathology. This will help us determine the molecular pathogenesis of MC proliferation and provide new targets for disease intervention.
Literature
2.
go back to reference Ah E. Mesangial cell biology. Exp Cell Res. 2012;318(9):978–85. Ah E. Mesangial cell biology. Exp Cell Res. 2012;318(9):978–85.
3.
go back to reference Morita TYY, Churg J. Mesangiolysis: an update. Am J Kidney Dis. 1993;31(4):559–73.CrossRef Morita TYY, Churg J. Mesangiolysis: an update. Am J Kidney Dis. 1993;31(4):559–73.CrossRef
4.
go back to reference Hartner A, Marek I, Cordasic N, Haas C, Schocklmann H, Hulsmann-Volkert G, et al. Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis. Am J Nephrol. 2008;28(1):168–78. doi:10.1159/000110022.CrossRefPubMed Hartner A, Marek I, Cordasic N, Haas C, Schocklmann H, Hulsmann-Volkert G, et al. Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis. Am J Nephrol. 2008;28(1):168–78. doi:10.​1159/​000110022.CrossRefPubMed
5.
go back to reference Shankland SJ, Hugo C, Coats SR, Nangaku M, Pichler RH, Gordon KL, et al. Changes in cell-cycle protein expression during experimental mesangial proliferative glomerulonephritis. Kidney Int. 1996;50(4):1230–9.CrossRefPubMed Shankland SJ, Hugo C, Coats SR, Nangaku M, Pichler RH, Gordon KL, et al. Changes in cell-cycle protein expression during experimental mesangial proliferative glomerulonephritis. Kidney Int. 1996;50(4):1230–9.CrossRefPubMed
6.
go back to reference Marti HP. Role of matrix metalloproteinases in the progression of renal lesions. Presse Med. 2000;29(14):811–7.PubMed Marti HP. Role of matrix metalloproteinases in the progression of renal lesions. Presse Med. 2000;29(14):811–7.PubMed
7.
go back to reference Sadlier DMOX, McMahon B, et al. Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis. Kidney Int. 2005;68(6):2542–61.CrossRefPubMed Sadlier DMOX, McMahon B, et al. Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis. Kidney Int. 2005;68(6):2542–61.CrossRefPubMed
9.
go back to reference Eitner F, Westerhuis R, Burg M, Weinhold B, Grone HJ, Ostendorf T, et al. Role of interleukin-6 in mediating mesangial cell proliferation and matrix production in vivo. Kidney Int. 1997;51(1):69–78.CrossRefPubMed Eitner F, Westerhuis R, Burg M, Weinhold B, Grone HJ, Ostendorf T, et al. Role of interleukin-6 in mediating mesangial cell proliferation and matrix production in vivo. Kidney Int. 1997;51(1):69–78.CrossRefPubMed
10.
11.
go back to reference Mori T, Shimizu A, Masuda Y, Fukuda Y, Yamanaka N. Hepatocyte growth factor-stimulating endothelial cell growth and accelerating glomerular capillary repair in experimental progressive glomerulonephritis. Nephron Exp Nephrol. 2003;94(2):e44–54. doi:10.1159/000071283.CrossRefPubMed Mori T, Shimizu A, Masuda Y, Fukuda Y, Yamanaka N. Hepatocyte growth factor-stimulating endothelial cell growth and accelerating glomerular capillary repair in experimental progressive glomerulonephritis. Nephron Exp Nephrol. 2003;94(2):e44–54. doi:10.​1159/​000071283.CrossRefPubMed
13.
go back to reference Stuart JSGW. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. Am J Physiol Renal Physiol. 2000;278:F515–29. Stuart JSGW. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. Am J Physiol Renal Physiol. 2000;278:F515–29.
14.
go back to reference Marti H. The role of matrix metalloproteinases in the activation of mesangial cells. Transpl Immunol. 2002;9:97–100.CrossRefPubMed Marti H. The role of matrix metalloproteinases in the activation of mesangial cells. Transpl Immunol. 2002;9:97–100.CrossRefPubMed
15.
go back to reference Maddika S, Ande SR, Panigrahi S, et al. Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy. Drug Resist Updates. 2007;10(1–2):13–29.CrossRef Maddika S, Ande SR, Panigrahi S, et al. Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy. Drug Resist Updates. 2007;10(1–2):13–29.CrossRef
16.
go back to reference Haas CSCV, Kuhlmann A, et al. Analysis of glomerular VEGF mRNA and protein expression in murine mesangioproliferative glomerulonephritis. Virchows Arch. 2007;450(1):81–92.CrossRefPubMed Haas CSCV, Kuhlmann A, et al. Analysis of glomerular VEGF mRNA and protein expression in murine mesangioproliferative glomerulonephritis. Virchows Arch. 2007;450(1):81–92.CrossRefPubMed
17.
go back to reference Nur R, Fukuda N, Matsumoto T, Medet J, Kano K, Yamamoto C, et al. Implantation of dedifferentiated fat cells ameliorates habu snake venom-induced chronic renal dysfunction in tenascin-C-deficient mice. Nephron Exp Nephrol. 2008;110(3):e91–8. doi:10.1159/000166995.CrossRefPubMed Nur R, Fukuda N, Matsumoto T, Medet J, Kano K, Yamamoto C, et al. Implantation of dedifferentiated fat cells ameliorates habu snake venom-induced chronic renal dysfunction in tenascin-C-deficient mice. Nephron Exp Nephrol. 2008;110(3):e91–8. doi:10.​1159/​000166995.CrossRefPubMed
18.
go back to reference Boer-Lima PA, Gontijo JA, Cruz-Hofling MA. Bothrops moojeni snake venom-induced renal glomeruli changes in rat. Am J Trop Med Hyg. 2002;67(2):217–22.PubMed Boer-Lima PA, Gontijo JA, Cruz-Hofling MA. Bothrops moojeni snake venom-induced renal glomeruli changes in rat. Am J Trop Med Hyg. 2002;67(2):217–22.PubMed
19.
go back to reference Hayashi W, Obata Y, Nishino T, Abe S, Io K, Furusu A, et al. Glomerular repair retardation via blocking of angiotensin II type 1a receptor pathway in a mouse glomerulonephritis model. Nephron Exp Nephrol. 2012;122(1–2):13–22. doi:10.1159/000346954.CrossRefPubMed Hayashi W, Obata Y, Nishino T, Abe S, Io K, Furusu A, et al. Glomerular repair retardation via blocking of angiotensin II type 1a receptor pathway in a mouse glomerulonephritis model. Nephron Exp Nephrol. 2012;122(1–2):13–22. doi:10.​1159/​000346954.CrossRefPubMed
20.
go back to reference Huang H, Wang H, Lu Y. Antisense to cyclin D1 inhibits the proliferation of glomerular mesangial cells. Zhonghua Yi Xue Za Zhi. 1998;78(4):293–5.PubMed Huang H, Wang H, Lu Y. Antisense to cyclin D1 inhibits the proliferation of glomerular mesangial cells. Zhonghua Yi Xue Za Zhi. 1998;78(4):293–5.PubMed
22.
go back to reference Lang SHA, Sterzel RB, et al. Requirement of CyclinD1 in Mesangial Cell Mitogenesis. J Am Soc Nephrol. 2000;11:1398–408.PubMed Lang SHA, Sterzel RB, et al. Requirement of CyclinD1 in Mesangial Cell Mitogenesis. J Am Soc Nephrol. 2000;11:1398–408.PubMed
23.
go back to reference Barnes JL, Hastings RR, De la Garza MA. Sequential expression of cellular fibronectin by platelets, macrophages, and mesangial cells in proliferative glomerulonephritis. Am J Pathol. 1994;145(3):585–97.PubMedPubMedCentral Barnes JL, Hastings RR, De la Garza MA. Sequential expression of cellular fibronectin by platelets, macrophages, and mesangial cells in proliferative glomerulonephritis. Am J Pathol. 1994;145(3):585–97.PubMedPubMedCentral
24.
go back to reference Nitta K, Horita S, Honda K, Uchida K, Watanabe T, Nihei H, et al. Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch. 1999;435(4):422–7.CrossRefPubMed Nitta K, Horita S, Honda K, Uchida K, Watanabe T, Nihei H, et al. Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch. 1999;435(4):422–7.CrossRefPubMed
25.
go back to reference Wang S, Kim JH, Moon KC, Hong HK, Lee HS. Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of focal segmental glomerulosclerosis. Am J Kidney Dis. 2004;43(1):19–27.CrossRefPubMed Wang S, Kim JH, Moon KC, Hong HK, Lee HS. Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of focal segmental glomerulosclerosis. Am J Kidney Dis. 2004;43(1):19–27.CrossRefPubMed
27.
go back to reference Marti HP. The role of matrix metalloproteinases in the activation of mesangial cells. Transpl Immunol. 2002;9(2–4):97–100.CrossRefPubMed Marti HP. The role of matrix metalloproteinases in the activation of mesangial cells. Transpl Immunol. 2002;9(2–4):97–100.CrossRefPubMed
28.
go back to reference Ju SM, Pae HO, Kim WS, Kang DG, Lee HS, Jeon BH. Role of reactive oxygen species in p53 activation during cisplatin-induced apoptosis of rat mesangial cells. Eur Rev Med pharmacol Sci. 2014;18(8):1135–41.PubMed Ju SM, Pae HO, Kim WS, Kang DG, Lee HS, Jeon BH. Role of reactive oxygen species in p53 activation during cisplatin-induced apoptosis of rat mesangial cells. Eur Rev Med pharmacol Sci. 2014;18(8):1135–41.PubMed
30.
go back to reference Kamyshova ES, Shvetsov M, Shestakov AE, Kutyrina IM, Nosikov VV. Association of gene TP53 polymorphic marker Pro72Arg with clinical characteristics of chronic glomerulonephritis. Ter Arkh. 2011;83(6):27–32.PubMed Kamyshova ES, Shvetsov M, Shestakov AE, Kutyrina IM, Nosikov VV. Association of gene TP53 polymorphic marker Pro72Arg with clinical characteristics of chronic glomerulonephritis. Ter Arkh. 2011;83(6):27–32.PubMed
31.
go back to reference Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281(5381):1305–8.CrossRefPubMed Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281(5381):1305–8.CrossRefPubMed
33.
go back to reference Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 2002;111(3):331–42.CrossRefPubMed Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 2002;111(3):331–42.CrossRefPubMed
Metadata
Title
Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis
Authors
Yang Lu
Jun Wen
DaPeng Chen
LingLing Wu
QingGang Li
Yuansheng Xie
Di Wu
Xiaoluan Liu
XiangMei Chen
Publication date
01-04-2016
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 2/2016
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-015-1163-6

Other articles of this Issue 2/2016

Clinical and Experimental Nephrology 2/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.