Zur Rolle von C5 und [alpha]5[beta]1-Integrin für die Entstehung von renaler Fibrose und mögliche therapeutische Konsequenzen

Tubulointerstitial fibrosis is the final stage of many progressive renal diseases. The aim of this study was to test new strategies of treatment in a mouse model which could be applied to clinical practise in future. We used C5-deficient-mice as well as specific C5aR-and alpha5beta1-Integrin antagonists to detect the influence of the anaphylatoxin C5a and alpha5beta1-Integrin in the development of renal tubulo-interstitial fibrosis. First, we induced a unilateral ureterobstruction (UUO) in C5 deficient mice and suitable wild type controls (as it is the standard model of tubulo-interstitial fibrosis in the mouse). In addition, C5aR-and alpha5beta1-Integrin antagonists were used in wild type mice next to control animals. On days 5 and 10 after UUO, animals were sacrified and kidneys were taken for histopathological examination. Markers for tubulointerstitial fibrosis (sirius red, fibronectin, collagene I, F4-80, alpha-smooth-muscle-actin) were stained and semi-quantified by conventional microscopy. In addition, the relative mRNA expression of all isoforms of the in most relevant growth factor in kidney diseases, PDGF, as well as some markers of epithelial mesenchymal transformation (E-cadherin, vimentin) and extra-cellular matrix proteins (collagen IV, fibronectin) were determined. As in C5-deficient mice as well as in animals treated with C5aR-anatgonist and/or integrin antagonist on day 5 a reduction of the markers for fibrosis could be recognized on the protein level and mRNA level. On day 10 after UUO this trend could be seen furthermore in some markers. In tubular cells with expression of the C5a receptor we could show in in-vitro experiments that the stimulation with recombinant C5a leaded to a significantly higher expression of pro- fibrotic TGF-beta. The presented results show the pro-fibrotic influence of C5a and alpha5beta1-integrin on the origin of tubulo-interstitial fibrosis More experiments are necessary to examine the underlying mechanisms of C5a-and alpha5beta1-integrin effects on renal fibrosis. There is hope that in future the application of C5aR-and/or alpha5beta1-integrin antagonists could be applied in chronical progressive kidney diseases as a therapy against tubulo-interstital fibrosis.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Schult, Anna Lisa

Contributors dc:contributor

• Flöge, Jürgen

• info:eu-repo/classification/ddc/610
• Fibrose
• Tierversuch
• Extrazelluläre Matrix
• Komplement <Immunologie>
• Mikroskopie
• Immuncytochemie
• Zellkultur
• Medizin
• Integrin
• UUO
• EMT
• mikroosmotische Pumnpe
• C5a
• complement
• fibrosis

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112812%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50261