gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Protein kinase C epsilon protects against high-glucose-induced renal fibrosis via a TGFbeta1-dependent mechanism in vivo

Protein kinase C-Epsilon schützt vor glukose-induzierter Nierenfibrose durch einen TGFbeta1-abhängigen Mechanismus in vivo

Meeting Abstract (Hypertonie 2004)

  • presenting/speaker M. Meier - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • J. Park - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • M. Holtz - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • J. Menne - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • F. Gueler - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • C. Lindschau - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • M. Leitges - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)
  • H. Haller - Medizinische Hochschule Hannover, MPI für Experimentelle Endokrinologie (Hannover, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP59

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch059.shtml

Veröffentlicht: 10. August 2005

© 2005 Meier et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

We have previously demonstrated that PKC-epsilon-expression was increased in the kidney from streptozotocin(STZ)-induced diabetic rats. In the present study, we tested the hypothesis that deletion of PKC-epsilon-expression in vivo will lead to protection against the development of murine experimental diabetic nephropathy.

We studied PKC-epsilon knock-out (KO) mice (n=11/5) compared to C57BL/6J wild type (WT) mice (n=9/8) in nondiabetic and diabetic condition. Hyperglycaemia was induced in 8 week old mice by intraperitoneal streptozotocin (STZ) injection(50 mg/kg/body weight on day 1 to 5). Diabetic mice (blood glucose > 20 mmol/l) remained hyperglycaemic (WT: 7.8 ± 0.9 vs. 20.3 ± 6.6 mmol/l and KO: 7.9 ± 1.1 vs. 22.1 ± 7.3 mmol/l). After 8 weeks animals were sacrificed and kidneys were removed.

Body weight in the non-diabetic groups was higher due to glucosuria in the diabetic groups. Urinary albumin/creatinine ratio was significantly increased in PKC-epsilon-KO mice compared to WT mice (10.4 vs. 36.2 g/mol) which was further exacerbated in diabetic (PKC-epsilon-KO) mice (11.5 vs. 140.1 g/mol) (p<0.5). Light microscopy showed more severe glomerular and tubulointerstitial fibrosis in diabetic PKC-epsilon KO compared to diabetic WT mice. Interestingly, the expected increased fibrosis in diabetic groups was already observed in PKC-epsilon KO mice under non-diabetic conditions while a significant increase of glomerular TGF-beta1 expression in PKC-epsilon KO compared to WT mice was further aggravated in the diabetic state. On the tubulointerstitial level, the expression of fibronectin and collagen IV as marker of renal fibrosis was also significantly increased in (diabetic) PKC-epsilon KO mice.

Our data suggest that PKC-epsilon expression is protective against renal fibrosis and that previously observed PKC-epsilon expression in the diabetic state may rather be a response-to-injury than a pathogenic effect itself.