TY  - JOUR
A1  - Zirafi, Onofrio
A1  - Kim, Kyeong-Ae
A1  - Ständker, Ludger
A1  - Mohr, Katharina B.
A1  - Sauter, Daniel
A1  - Heigele, Anke
A1  - Kluge, Silvia F.
A1  - Wiercinska, Eliza
A1  - Chudziak, Doreen
A1  - Richter, Rudolf
A1  - Möpps, Barbara
A1  - Gierschik, Peter
A1  - Vas, Virag
A1  - Geiger, Hartmut
A1  - Lamla, Markus
A1  - Weil, Tanja
A1  - Burster, Timo
A1  - Zgraja, Andreas
A1  - Daubeuf, Francois
A1  - Frossard, Nelly
A1  - Hachet-Haas, Muriel
A1  - Heunisch, Fabian
A1  - Reichetzeder, Christoph
A1  - Galzi, Jean-Luc
A1  - Perez-Castells, Javier
A1  - Canales-Mayordomo, Angeles
A1  - Jimenez-Barbero, Jesus
A1  - Gimenez-Gallego, Guillermo
A1  - Schneider, Marion
A1  - Shorter, James
A1  - Telenti, Amalio
A1  - Hocher, Berthold
A1  - Forssmann, Wolf-Georg
A1  - Bonig, Halvard
A1  - Kirchhoff, Frank
A1  - Münch, Jan
T1  - Discovery and Characterization of an Endogenous CXCR4 Antagonist
JF  - Cell reports
N2  - CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Y1  - 2015
U6  - https://doi.org/10.1016/j.celrep.2015.03.061
SN  - 2211-1247
VL  - 11
IS  - 5
SP  - 737
EP  - 747
PB  - Cell Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Dschietzig, Thomas Bernd
A1  - Krause-Relle, Katharina
A1  - Hennequin, Maud
A1  - von Websky, Karoline
A1  - Rahnenfuhrer, Jan
A1  - Ruppert, Jana
A1  - Groena, Hans Juergen
A1  - Armbruster, Franz Paul
A1  - Bathgate, Ross A. D.
A1  - Aschenbach, Joerg R.
A1  - Forssmann, Wolf-Georg
A1  - Hocher, Berthold
T1  - Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
KW  - Diabetic nephropathy
KW  - Diabetic cardiomyopathy
KW  - Fibrosis
KW  - Inflammation
KW  - Relaxin
Y1  - 2015
U6  - https://doi.org/10.1159/000368484
SN  - 1420-4096
SN  - 1423-0143
VL  - 40
IS  - 1
SP  - 77
EP  - 88
PB  - Karger
CY  - Basel
ER  -