br Results br Discussion DDR mice

Results
Discussion DDR−/− mice develop a mild renal phenotype without renal failure and without severe proteinuria (Gross et al. 2004b). Their local defect of the GBM affected less than 2% of the total GBM-area only. Further, their mild renal phenotype showed up later in life (6 to 9months of age) compared to the two to three month old Double-knockout mice used in the present study. Our findings on the collagen-receptor DDR1 are in accordance to a previous study by Cosgrove and coworkers about the collagen-receptor α1/β1 integrin (Cosgrove et al., 2000). The present study further reinforces the role of the collagen-receptor DDR1 in chronic renal fibrosis by improving the hard end point lifespan until death from renal failure. Additionally, the localization of the collagen-receptor DDR1 at the lateral RWJ 56110 of podocytes points to an important role of DDR1 in matrix–cell interaction between GBM and podocyte. Activation of DDR1 requires a transmembrane leucine zipper (Noordeen et al., 2006) and four neighboring, surface-exposed collagen-loops (Abdulhussein et al., 2008). These collagen-loops can be altered by glycine mutations in AS. AS patients with a 3′ glycine mutation develop a different phenotype than patients with 5′ glycine mutations (Gross et al., 2002). Different mutated collagen-loops might result in different binding affinity to collagen receptors such as DDR1. Therefore, DDR1 seems to play an important role in pathogenesis of AS. Abrahamson and coworkers (2009) recently demonstrated a distinct role of the podocyte in preservation and production of mature GBM-components such as α3/4/5(IV)-chains. This group further verified that collagen receptors (integrins) are linked to the cytoskeleton of podocytes. In accordance to this data, our study points to a similar function of DDR1 in maintenance of podocyte\'s cytoskeleton and architecture (Fig. 2). This function of DDR1 seems not to rely on integrin-signaling, as DDR1 is activated independently from integrins (Vogel et al., 2000).
Experimental procedures
Acknowledgements The authors want to thank the staff of the animal facilities at the Center of Molecular Medicine Cologne, at the MPI Experimental Medicine Goettingen and the Medical Faculty of the University of Goettingen for animal care. We thank Mrs. Andrea Bernhard and Mrs. Oya Goektas for excellent technical assistance. Parts of this work were presented as abstracts at the annual meetings of the German and the American Societies of Nephrology. This work was supported by grants from the Kidney Foundation of Canada (W.F.V.), the Cologne Fortune Program (O.G.) and is supported by the Deutsche Forschungsgemeinschaft DFGGR 1852/4-1 and 4-2 (O.G.).
Introduction Insects dominate on earth, it is estimated that more than one million insects have been taxonomically identified. Previous investigations indicate that structurally novel and biological non-peptide small molecules (NPSMs) are present in insects [1], [2]. However, small molecules from insects and their roles in Nature, unlike plant or microorganism metabolites, are largely unknown. We became interested in insect metabolites and characterized a series of NPSMs from several insects [3], [4], [5], [6], [7]. Polyphaga plancyi Bolivar, a widely distributed insect species in China with blood stasis removing properties, has been used as a traditional Chinese medicine to treat a wide range of diseases such as amenorrhea and fracture. Modern pharmacological studies show that its extract possesses wide effects such as anticancer and anti-inflammatory properties [8]. In the course of our continuing study on insect NPSMs, the title insect were investigated, which led to the isolation of 8 NPSMs including five ones are new compounds (Fig. 1). Herein, we report their isolation, structure characterization and biological evaluation.