Universität zu Köln

Braehler, Sebastian, Ising, Christina ORCID: 0000-0002-7267-3488, Aranda, Belen Barrera, Hoehne, Martin, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas and Brinkkoetter, Paul Thomas (2015). The NF-kappa B essential modulator (NEMO) controls podocyte cytoskeletal dynamics independently of NF-kappa B. Am. J. Physiol.-Renal Physiol., 309 (7). S. F617 - 10. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1466

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Abstract

Maintenance of the glomerular filtration barrier with its fenestrated endothelium, the glomerular basement membrane, and the podocytes as the outer layer, is a major prerequisite for proper renal function. Tight regulation of the balance between plasticity and rigidity of the podocytes' architecture is required to prevent the onset of glomerular disease, mainly proteinuria. The underlying cellular signaling pathways that regulate the organization of the podocytes' cytoskeleton are still a matter of controversial debate. In this study, we investigated the role of the NF-kappa B signaling pathway in podocyte cytoskeletal dynamics. As previously published, genetic inhibition of the NF-kappa B essential modulator (NEMO) in podocytes does not affect glomerular function under physiological, nonstressed conditions nor does it alter the initial podocyte response in an experimental glomerulonephritis (NTN) model (Brahler S, Ising C, Hagmann H, Rasmus M, Hoehne M, Kurschat C, Kisner T, Goebel H, Shankland SJ, Addicks K, Thaiss F, Schermer B, Pasparakis M, Benzing T, Brinkkoetter PT. Am J Physiol Renal Physiol 303: F1473-F1475, 2012). Quite the contrary, podocyte-specific NEMO null mice recovered significantly faster and did not develop glomerulosclerosis and end- stage renal failure over time. Here, we show that cytoskeletal rearrangements and increased podocyte motility following stimulation with IL-1, TNF-alpha, or LPS depend on NEMO. NEMO also regulates the phosphorylation of the MAP kinase ERK1/2 and suppresses the activation of RhoA following stimulation with IL-1. The migratory response and altered ERK1/2 phosphorylation is independent of NF-kappa B signaling as demonstrated by expression of a mutant I kappa B resistant to phosphorylation and degradation. In conclusion, signaling through NEMO might not only be involved in the production of NF-kappa B proinflammatory chemokines but also regulates podocyte dynamics independently of NF-kappa B, most likely through small GTPases and MAP kinases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Braehler, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ising, Christina UNSPECIFIED orcid.org/0000-0002-7267-3488 UNSPECIFIED Aranda, Belen Barrera UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoehne, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391492
DOI:	10.1152/ajprenal.00059.2015
Journal or Publication Title:	Am. J. Physiol.-Renal Physiol.
Volume:	309
Number:	7
Page Range:	S. F617 - 10
Date:	2015
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1466
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CELL-MIGRATION; UROKINASE RECEPTOR; KIDNEY PODOCYTES; PROTEINURIA; RAC1; MICE; IDENTIFICATION; EXPRESSION; PROTECTS Multiple languages Physiology; Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39149