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

BMC Nephrology

Research Article

Karl Swärd¹  Katarzyna K. Krawczyk¹  Jennifer Hansson²  Martin E. Johansson³  Krzysztof M. Krawczyk³  Helén Nilsson³ 

[1] Department of Experimental Medical Science, Lund University, Lund, Sweden;Department of Laboratory Medicine, Lund University, Lund, Sweden;Department of Translational Medicine, Clinical Pathology, Lund University, SUS Malmö, Jan Waldenströms gata 59, SE-20502, Malmö, Sweden;

关键词: Caveolae;    Caveolin;    Cavin;    Kidney fibrosis;    MKL1;    FLNA;    SCAI;   

DOI  :  10.1186/s12882-017-0738-8

 received in 2016-11-11, accepted in 2017-09-25,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCaveolae 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.MethodsHealthy 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.ResultsIn 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017