![]() ![]() ![]() 1 NS is classified by response or nonresponse to a standardized glucocorticosteroid therapy as steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. ![]() Childhood NS, if untreated, is associated with increased risk of life-threatening infections, thromboembolism, lipid abnormalities, and malnutrition. Nephrotic syndrome (NS) is a CKD defined by nephrotic-range proteinuria caused by disruption of the renal glomerular filtration barrier, resulting in hypoalbuminemia, hyperlipidemia, and edema. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. This phenotype was partially rescued by glucocorticoids. We found that loss of emp2 in zebrafish upregulated caveolin-1 ( cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease–based genome editing. We previously identified mutations in epithelial membrane protein 2 ( EMP2) as a monogenic cause of this disease. Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. ![]()
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