Universität zu Köln

Fries, Jochen W. U. (2019). MicroRNAs as markers to monitor endothelin-1 signalling and potential treatment in renal disease: Carcinoma - proteinuric damage - toxicity. Biol. Cell, 111 (7). S. 169 - 187. HOBOKEN: WILEY. ISSN 1768-322X

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Abstract

This review highlights new developments in miRNA as diagnostic and surveillance tools in diseases damaging the renal proximal tubule mediated by endothelin in the field of renal carcinoma, proteinuric kidney disease and tubulotoxicity. A new mechanism in the miRNA regulation of proteins leads to the binding of the miRNA directly to the DNA with premature transcriptional termination and hence the formation of truncated protein isoforms (Mxi2, Vim3). These isoforms are mediated through miRNA15a or miRNA 498, respectively. ET-1 can activate a cytoplasmic complex consisting of NF-kappa B p65, MAPK p38 alpha, and PKC alpha. Consequently, PKC alpha does not transmigrate into the nucleus, which leads to the loss of suppression of a primiRNA15a, maturation of this miRNA in the cytoplasm, tubular secretion and detectability in the urine. This mechanism has been shown in renal cell carcinoma and in proteinuric disease as a biomarker for the activation of the signalling pathway. Similarly, ET-1 induced miRNA 498 transmigrates into the nucleus to form the truncated protein Vim3, which is a biomarker for the benign renal cell tumour, oncocytoma. In tubulotoxicity, ET-1 induced miRNa133a down-regulating multiple-drug-resistant related protein-2, relevant for proteinuric and cisplatin/cyclosporine A toxicity. Current advantages and limitations of miRNAs as urinary biomarkers are discussed.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fries, Jochen W. U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136514
DOI:	10.1111/boc.201800059
Journal or Publication Title:	Biol. Cell
Volume:	111
Number:	7
Page Range:	S. 169 - 187
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1768-322X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; TUBULAR EPITHELIAL-CELLS; KINASE-C-ALPHA; ANGIOTENSIN-II; TRANSCRIPTIONAL REGULATION; URINARY ENDOTHELIN-1; CYCLOSPORINE-A; SERUM MIR-210; EXPRESSION; RECEPTOR Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13651