Universität zu Köln

Burford, James L., Villanueva, Kane, Lam, Lisa, Riquier-Brison, Anne, Hackl, Matthias J., Pippin, Jeffrey, Shankland, Stuart J. and Peti-Peterdi, Janos ORCID: 0000-0003-4092-6185 (2014). Intravital imaging of podocyte calcium in glomerular injury and disease. J. Clin. Invest., 124 (5). S. 2050 - 2059. ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 1558-8238

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Abstract

Intracellular calcium ([Ca-2i](i)) signaling mediates physiological and pathological processes in multiple organs, including the renal podocyte; however, in vivo podocyte [Ca-2i](i) dynamics are not fully understood. Here we developed an imaging approach that uses multiphoton microscopy (MPM) to directly visualize podocyte [Ca-2i](i) dynamics within the intact kidneys of live mice expressing a fluorescent calcium indicator only in these cells. [Ca-2i](i) was at a low steady-state level in control podocytes, while Ang II infusion caused a minor elevation. Experimental focal podocyte injury triggered a robust and sustained elevation of podocyte [Ca-2i](i) around the injury site and promoted cell-to-cell propagating podocyte [Ca-2i](i) waves along capillary loops. [Ca-2i](i) wave propagation was ameliorated by inhibitors of purinergic [Ca-2i](i) signaling as well as in animals lacking the P2Y2 purinergic receptor. Increased podocyte [Ca-2i](i) resulted in contraction of the glomerular tuft and increased capillary albumin permeability. In preclinical models of renal fibrosis and glomerulosclerosis, high poclocyte [Ca-2i](i) correlated with increased cell motility. Our fmdings provide a visual demonstration of the in vivo importance of pod.ocyte [Ca-2i](i) in glomerular pathology and suggest that purinergic [Ca-2i](i) signaling is a robust and key pathogenic mechanism in pod.ocyte injury. This in vivo imaging approach will allow future detailed investigation of the molecular and cellular mechanisms of glomerular disease in the intact living kidney.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Burford, James L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Villanueva, Kane UNSPECIFIED UNSPECIFIED UNSPECIFIED Lam, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Riquier-Brison, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackl, Matthias J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pippin, Jeffrey UNSPECIFIED UNSPECIFIED UNSPECIFIED Shankland, Stuart J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peti-Peterdi, Janos UNSPECIFIED orcid.org/0000-0003-4092-6185 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440084
DOI:	10.1172/JCI71702
Journal or Publication Title:	J. Clin. Invest.
Volume:	124
Number:	5
Page Range:	S. 2050 - 2059
Date:	2014
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	1558-8238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUBULOGLOMERULAR FEEDBACK; MULTIPHOTON MICROSCOPY; URETERAL OBSTRUCTION; ACTIN CYTOSKELETON; EPITHELIAL-CELLS; TRANSGENIC MICE; TRPC6 CHANNELS; IN-VIVO; KIDNEY; FILTRATION Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44008