Universität zu Köln

Spaeth, Martin R., Bartram, Malte P., Palacio-Escat, Nicolas ORCID: 0000-0002-7022-1437, Hoyer, K. Johanna R., Debes, Cedric, Demir, Fatih ORCID: 0000-0002-5744-0205, Schroeter, Christina B., Mandel, Amrei M., Grundmann, Franziska, Ciarimboli, Giuliano, Beyer, Andreas ORCID: 0000-0002-3891-2123, Kizhakkedathu, Jayachandran N., Brodesser, Susanne, Goebel, Heike, Becker, Jan U., Benzing, Thomas, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Hoehne, Martin, Burst, Volker, Saez-Rodriguez, Julio ORCID: 0000-0002-8552-8976, Huesgen, Pitter F., Mueller, Roman-Ulrich and Rinschen, Markus M. (2019). The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney Int., 95 (2). S. 333 - 350. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Acute kidney injury (AKI) leads to significant morbidity and mortality; unfortunately, strategies to prevent or treat AKI are lacking. In recent years, several preconditioning protocols have been shown to be effective in inducing organ protection in rodent models. Here, we characterized two of these interventions-caloric restriction and hypoxic preconditioning-in a mouse model of cisplatin-induced AKI and investigated the underlying mechanisms by acquisition of multi-layered omic data (transcriptome, proteome, N-degradome) and functional parameters in the same animals. Both preconditioning protocols markedly ameliorated cisplatin-induced loss of kidney function, and caloric restriction also induced lipid synthesis. Bioinformatic analysis revealed mRNA-independent proteome alterations affecting the extracellular space, mitochondria, and transporters. Interestingly, our analyses revealed a strong dissociation of protein and RNA expression after cisplatin treatment that showed a strong correlation with the degree of damage. N-degradomic analysis revealed that most posttranscriptional changes were determined by arginine-specific proteolytic processing. This included a characteristic cisplatin-activated complement signature that was prevented by preconditioning. Amyloid and acute-phase proteins within the cortical parenchyma showed a similar response. Extensive analysis of disease-associated molecular patterns suggested that transcription-independent deposition of amyloid P-component serum protein may be a key component in the microenvironmental contribution to kidney damage. This proof-of-principle study provides new insights into the pathogenesis of cisplatin-induced AKI and the molecular mechanisms underlying organ protection by correlating phenotypic and multi-layered omics data.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Spaeth, Martin R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartram, Malte P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Palacio-Escat, Nicolas UNSPECIFIED orcid.org/0000-0002-7022-1437 UNSPECIFIED Hoyer, K. Johanna R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Debes, Cedric UNSPECIFIED UNSPECIFIED UNSPECIFIED Demir, Fatih UNSPECIFIED orcid.org/0000-0002-5744-0205 UNSPECIFIED Schroeter, Christina B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mandel, Amrei M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grundmann, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Ciarimboli, Giuliano UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Kizhakkedathu, Jayachandran N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Goebel, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Hoehne, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Burst, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Saez-Rodriguez, Julio UNSPECIFIED orcid.org/0000-0002-8552-8976 UNSPECIFIED Huesgen, Pitter F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-158363
DOI:	10.1016/j.kint.2018.08.037
Journal or Publication Title:	Kidney Int.
Volume:	95
Number:	2
Page Range:	S. 333 - 350
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; EXTRACELLULAR-MATRIX; RENAL FIBROSIS; N-TERMINI; ISCHEMIA; ACTIVATION; MECHANISMS; RESTRICTION; ASSOCIATION; INHIBITION Multiple languages Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15836