Abstract
Chronic kidney disease (CKD) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (GFB). GFB is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes. CKD with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement. Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer. Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in CKD. Experiments were carried out on Drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte. Furthermore, the survival rate of gelsolin-knocked down Drosophila larvae was extensively reduced after AgNO3 exposure. Secondly, the in vitro podocytes treated with puromycin aminonucleoside (PAN) enhanced the gelsolin protein expression, as well as small GTPase RhoA and Rac1, which also regulated actin dynamic expression incrementally with the PAN concentrations. Thirdly, we further demonstrated in vivo that GSN was highly expressed inside the glomeruli with mitochondrial dysfunction in a CKD mouse model. Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli.
Highlights
Chronic kidney disease (CKD) is a significant public health problem on a global scale.Kidney function impairment can result in substantial morbidity [1] and CKD is strongly associated with cardiovascular diseases and is a leading cause of death [2]
Results a Ca2+ channel known as the Transient Receptor Potential Cation Channel 6 (TRPC6), which has been observed in proteinuria kidney disease [12]
Gelsolin Is Requiretod afsocreMrtaaininhtoawinigneglsoNlienprhergouclyatesFcuyntocstkioelnetionnDasrsoesmopblhyi,lsapecifically actin assembly, in Drosophila nepphordooccyytteess daucrtinags chheromnioclkyimdnpeyhinfijlutreyrsp.roDceusesetso. the fact that nephrocytes are capable of remov2i.nRgestuolxtsins such as silver nitrate (AgNO3) from hemolymph [7], we investigated whethe2r.1g. eGleslosolliinn IissRreqeuqiureidrfeodr MfoairntnaienpinhgrNoecpyhtreocyttoexFiunncrteiomn ionvDarlosfoupnhiclation to be maintained
Summary
Kidney function impairment can result in substantial morbidity [1] and CKD is strongly associated with cardiovascular diseases and is a leading cause of death [2]. CKD patients are more likely to develop peripheral arterial occlusion disease (PAOD). PAOD was found to be significantly associated with low eGFR, low BMI, and high blood pressure in a study of elderly people from the Tianliao area. The glomerular filtration barrier (GFB) is made up of fenestrated endothelial cells that line the capillary loops, a specialized glomerular basement membrane (GBM), and podocytes that line the GFB’s exterior [2,4]. The glomerular filtration barrier in the kidney is formed by podocytes, endothelial cells, and the basement membrane [5]
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