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SFB 1192

Project B10

Proteolytic control of immune-mediated kidney diseases

Proteolytic events are key processes in initiation and propagation of glomerular kidney diseases. More than 500 proteases are encoded in the human genome and are regarded as an attractive drug target in inflammation. Both extracellular and intracellular proteases are tightly interconnected and from a proteolytic web that controls glomerular disease progression in inflammation. However, details on their signaling and activation in the proteolytic microenvironment in glomerular inflammation are missing.  Here, we propose a systems approach to glomerular inflammatory disease processes on the proteome level in order to pinpoint mechanisms of proteolytic action in glomerular inflammation, and to apply information of novel proteolytic signatures to prognosis in patients with glomerular kidney disease. In particular, we will 1) analyze how proteolytic signals are propagated over time in different models of glomerular inflammation 2) how proteases are activated and secreted in glomerular disease, and 3) what role novel proteolytic fragments play for the outcome of glomerular inflammation. Together, we will pioneer improved diagnosis, and finally, management of patients with inflammatory glomerular disease.

Selected Publications:

Amino acid metabolism in kidney health and disease.

Knol MGE, Wulfmeyer VC, Müller RU, Rinschen MM.
Nat Rev Nephrol. 2024 Aug

Metabolic Communication by SGLT2 Inhibition.

Billing AM, Kim YC, Gullaksen S, Schrage B, Raabe J, Hutzfeldt A, Demir F, Kovalenko E, Lassé M, Dugourd A, Fallegger R, Klampe B, Jaegers J, Li Q, Kravtsova O, Crespo-Masip M, Palermo A, Fenton RA, Hoxha E, Blankenberg S, Kirchhof P, Huber TB, Laugesen E, Zeller T, Chrysopoulou M, Saez-Rodriguez J, Magnussen C, Eschenhagen T, Staruschenko A, Siuzdak G, Poulsen PL, Schwab C, Cuello F, Vallon V, Rinschen MM.
Circulation. 2024 Mar

An integrated organoid omics map extends modeling potential of kidney disease.

Lassé M, El Saghir J, Berthier CC, Eddy S, Fischer M, Laufer SD, Kylies D, Hutzfeldt A, Bonin LL, Dumoulin B, Menon R, Vega-Warner V, Eichinger F, Alakwaa F, Fermin D, Billing AM, Minakawa A, McCown PJ, Rose MP, Godfrey B, Meister E, Wiech T, Noriega M, Chrysopoulou M, Brandts P, Ju W, Reinhard L, Hoxha E, Grahammer F, Lindenmeyer MT, Huber TB, Schlüter H, Thiel S, Mariani LH, Puelles VG, Braun F, Kretzler M, Demir F, Harder JL, Rinschen MM.
Nat Commun. 2023 Aug

Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension.

Rinschen MM, Palygin O, El-Meanawy A, Domingo-Almenara X, Palermo A, Dissanayake LV, Golosova D, Schafroth MA, Guijas C, Demir F, Jaegers J, Gliozzi ML, Xue J, Hoehne M, Benzing T, Kok BP, Saez E, Bleich M, Himmerkus N, Weisz OA, Cravatt BF, Krüger M, Benton HP, Siuzdak G, Staruschenko A.
Nat Commun. 2022 Jul

Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis.

Koehler S, Kuczkowski A, Kuehne L, Jüngst C, Hoehne M, Grahammer F, Eddy S, Kretzler M, Beck BB, Höhfeld J, Schermer B, Benzing T, Brinkkoetter PT, Rinschen MM.
J Am Soc Nephrol. 2020 Mar

 

Project-Team

Project Leader
Prof. Markus Rinschen

Co-Workers
Dr. rer. nat. Moritz Lassé
Dr. med. Birte Wöhner
Lars Nilges
Arvid Hutzfeldt
Stefan Gatzemeier