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BMC Nephrology
Published in: BMC Nephrology 1/2017

Open Access 01-12-2017 | Research article

Injury induced expression of caveolar proteins in human kidney tubules - role of megakaryoblastic leukemia 1

Authors: Krzysztof M. Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K. Krawczyk, Karl Swärd, Martin E. Johansson

Published in: BMC Nephrology | Issue 1/2017

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Abstract

Background

Caveolae are membrane invaginations measuring 50–100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined.

Methods

Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1–3 and cavin 1–4) and examined by electron microscopy. Induction of caveolar proteins was studied in isolated proximal tubules and primary renal epithelial cells. These cells were challenged with hypoxia or H2O2. Primary tubular cells were also subjected to viral overexpression of megakaryoblastic leukemia 1 (MKL1) and MKL1 inhibition by the MKL1 inhibitor CCG-1423. Putative coregulators of MKL1 activity were investigated by Western blotting for suppressor of cancer cell invasion (SCAI) and filamin A (FLNA). Finally, correlative bioinformatic studies of mRNA expression of caveolar proteins and MKL1 were performed.

Results

In healthy kidneys, caveolar proteins were expressed by the parietal epithelial cells (PECs) of Bowman’s capsule, endothelial cells and vascular smooth muscle. Electron microscopy confirmed caveolae in the PECs. No expression was seen in proximal tubules. In contrast, caveolar proteins were expressed in proximal tubules undergoing atrophy. Caveolar proteins were also induced in cultures of primary epithelial tubular cells. Expression was not enhanced by hypoxia or free radical stress (H2O2), but proved sensitive to inhibition of MKL1. Viral overexpression of MKL1 induced caveolin-1/CAV1, caveolin-2/CAV2 and SDPR/CAVIN2. In kidney tissue, the mRNA level of MKL1 correlated with the mRNA levels for caveolin-1/CAV1, caveolin-2/CAV2 and the archetypal MKL1 target tenascin C (TNC), as did the MKL1 coactivator FLNA. Costaining for TNC as readout for MKL1 activity demonstrated overlap with caveolin-1/CAV1 expression in PECs as well as in atrophic segments of proximal tubules.

Conclusions

Our findings support the view that MKL1 contributes to the expression of caveolar proteins in healthy kidneys and orchestrates the induction of tubular caveolar proteins in renal injury.
Appendix
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Metadata
Title
Injury induced expression of caveolar proteins in human kidney tubules - role of megakaryoblastic leukemia 1
Authors
Krzysztof M. Krawczyk
Jennifer Hansson
Helén Nilsson
Katarzyna K. Krawczyk
Karl Swärd
Martin E. Johansson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2017
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-017-0738-8

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