Abstract
APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin.
Highlights
Apolipoprotein L1 (APOL1) is one of six gene members of the apolipoprotein L family in humans that are clustered on chromosome 22
ZApoL1 is expressed in podocytes and endothelium in the zebrafish pronephros
Since edema formation is a hallmark of a leaky glomerular filtration barrier, we studied the effect of the Zebrafish ApoL1 (zApoL1) KD on the glomerulus by using H&E stained sections of zebrafish larvae (4 dpf)
Summary
Apolipoprotein L1 (APOL1) is one of six gene members of the apolipoprotein L family in humans that are clustered on chromosome 22. Two transcript variants of APOL1 encoding for two isoforms have been identified. One isoform contains beside the typical functional domains of the APOL family—the MAD, BH3, PFD and SRA domain—a secretory signal domain (S), which confers resistance to Trypanosoma bruci [1,2,3]. Studies have shown that APOL1, a BH3-only lipid-binding protein, induces autophagy and apoptosis (Zhaorigetu et al 2008). It has been published that three variants in the coding sequence of the APOL1 gene.
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