Keratine in der Niere, endogene zytoprotektive Faktoren?

• Antragsteller: Professor Peter Boor, Ph.D.
• Fachliche Zuordnung: Nephrologie ; Pathologie
• Förderung: Förderung von 2016 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 318056912

Zusammenfassung der Projektergebnisse

Keratins (K) are a major component of the cell cytoskeleton of epithelial cells, providing for their mechanical integrity. Keratins also have protective functions in a variety of stress situations and diseases, best described for skin and the gastrointestinal tract. Tubular cells (TEC) are the most abundant kidney epithelial cells. During virtually all kidney diseases TEC are exposed to a number of stress stimuli. We showed that the major renal keratins are highly up-regulated in different animal models and patients with kidney diseases and could thereby serve as novel markers (i.e. diagnostic test) of TEC stress. We could substantiate these findings in different application scenarios. In ongoing work we also showed the regulation of previously unrecognized keratins in the kidneys, and showed the potential of a specific keratin, K18, and its fragments, as a potential diagnostic (serum or urinary) marker of kidney diseases in patients. Besides, the application helped us to provide scientific contribution and insights into chronic kidney diseases and renal fibrosis, specific kidney diseases and development of novel models, tissue diseases biomarker and non-invasive in vivo imaging, AI and deep learning augmented pathology diagnostics and a number of other studies. The project is in part followed in the recently established Clinical Research Unit 5011. Overall, our data suggest that keratins might be useful biomarkers of kidney tissue injury.

Projektbezogene Publikationen (Auswahl)

• HIF stabilization inhibits renal epithelial cell migration and is associated with cytoskeletal alterations. Sci Rep 2018, 8:9497
  Müller S, Djudjaj S, Lange J, Iacovescu M, Goppelt-Struebe M, Boor P
  
• The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery. Sci Transl Med 2018, 10:eaan4886
  Stoppe C, Averdunk L, Goetzenich A, Soppert J, Marlier A, Kraemer S, Vieten J, Coburn M, Stevanovic A, Kim B-S, Marx G, Rex S, Ochi A, Leng L, Moeckel G, Linkermann A, El Bounkari O, Zarbock A, Bernhagen J, Djudjaj S, Bucala R, Boor P
  
• Elastin imaging enables non-invasive staging and treatment monitoring of kidney fibrosis. Sci Transl Med 2019, 11:eaat4865
  Sun Q, Baues M, Klinkhammer BM, Ehling J, Djudjaj S, Drude NI, Daniel C, Amann K, Kramann R, Kim H, Saez-Rodriguez J, Weiskirchen R, Onthank DC, Botnar RM, Kiessling F, Floege J, Lammers T, Boor P
  
• Cellular and molecular mechanisms of kidney injury in 2,8-dihydroxyadenine nephropathy. J Am Soc Nephrol 2020, 31:799-816
  Klinkhammer BM, Djudjaj S, Kunter U, Palsson R, Edvardsson VO, Wiech T, Thorsteinsdottir M, Hardarson S, Foresto-Neto O, Mulay SR, Moeller MJ, Jahnen- Dechent W, Floege J, Anders HJ, Boor P
  
• Collagen-specific molecular imaging of renal fibrosis. Kidney Int. 2020, 97:609-614
  Baues M, Klinkhammer BM, Ehling J, Gremse F, van Zandvoort MAMJ, Reutelingsperger CPM, Daniel C, Amann K, Bábíčková J, Kiessling F, Floege J, Lammers L, Boor P
  
• Crystal clots as therapeutic target in cholesterol crystal embolism. Circulation Research 2020, 126:e37-e52
  Shi C, Kim T, Steiger S, Mulay SR, Klinkhammer BM, Bäuerle T, Melica ME, Romagnani P, Möckel D, Baues M, Yang L, Mammadova-Bach E, Sanne B, Heemskerk JWM, Braun A, Lammers T, Boor P, Anders HJ
  
• Dysregulated mesenchymal PDGFR-β drives kidney fibrosis. EMBO Mol Med 2020, 12:e11021
  Buhl EM, Djudjaj S, Klinkhammer BM, Ermert K, Puelles VG, Lindenmeyer MT, Cohen CD, He C, Borkham-Kamphorst E, Weiskirchen R, Denecke B, Trairatphisan P, Saez- Rodriguez J, Huber TB, Olson LE, Floege J, Boor P
  
• Decoding myofibroblast origin in human kidney fibrosis. Nature 2021, 589:281-286
  Kuppe C, Ibrahim M, Kranz J, Zhang X, Ziegler S, Jansen J, Reimer K, Peraales J, Smith R, Dobie R, Wilson-Kanamari J, Halder M, Xu Y, Kabgani N, Kaesler N, Klaus M, Gernhold L, Puelles V, Huber T, Boor P, Menzel S, Hoogenboezem R, Bindels E, Steffens J, Floege J, Schneider R, Saez-Rodriguez J, Henderson S, Kramann R
  
• Deep Learning-Based Segmentation and Quantification in Experimental Kidney Histopathology. J Am Soc Nephrol. 2021, 32:52-68
  Bouteldja N, Klinkhammer BM, Bülow RD, Droste P, Otten SW, Freifrau von Stillfried S, Moellmann J, Sheehan SM, Korstanje R, Menzel S, Bankhead P, Mietsch M, Drummer C, Lehrke M, Kramann R, Floege J, Boor P, Merhof D