Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200583373> ?p ?o ?g. }
- W4200583373 abstract "We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking the steroid responsiveness observed in patients with SSNS. The p.H310Y variant also disrupted binding of clavesin-1 to α-tocopherol transfer protein, resulting in increased reactive oxygen species (ROS) accumulation in CLVS1-deficient podocytes. Treatment of CLVS1-knockout or homozygous H310Y-knockin podocytes with pharmacological ROS inhibitors restored viability to control levels. Taken together, these data identify CLVS1 as a candidate gene for SSNS, provide insight into therapeutic effects of corticosteroids on podocyte cellular dynamics, and add to the growing evidence of the importance of endocytosis and oxidative stress regulation to podocyte function." @default.
- W4200583373 created "2021-12-31" @default.
- W4200583373 creator A5001436579 @default.
- W4200583373 creator A5003145576 @default.
- W4200583373 creator A5010024932 @default.
- W4200583373 creator A5013495889 @default.
- W4200583373 creator A5013722838 @default.
- W4200583373 creator A5016313952 @default.
- W4200583373 creator A5018422509 @default.
- W4200583373 creator A5018819198 @default.
- W4200583373 creator A5021750333 @default.
- W4200583373 creator A5029478274 @default.
- W4200583373 creator A5031820791 @default.
- W4200583373 creator A5048514549 @default.
- W4200583373 creator A5050651187 @default.
- W4200583373 creator A5070873955 @default.
- W4200583373 creator A5078947409 @default.
- W4200583373 creator A5079146912 @default.
- W4200583373 creator A5088279493 @default.
- W4200583373 date "2022-01-25" @default.
- W4200583373 modified "2023-10-08" @default.
- W4200583373 title "Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis" @default.
- W4200583373 cites W1524607854 @default.
- W4200583373 cites W1597344058 @default.
- W4200583373 cites W1919257374 @default.
- W4200583373 cites W1964324684 @default.
- W4200583373 cites W1965979431 @default.
- W4200583373 cites W1968005976 @default.
- W4200583373 cites W1969327161 @default.
- W4200583373 cites W1969996031 @default.
- W4200583373 cites W1981308965 @default.
- W4200583373 cites W1987754412 @default.
- W4200583373 cites W1996099843 @default.
- W4200583373 cites W1999977358 @default.
- W4200583373 cites W2002927783 @default.
- W4200583373 cites W2005188572 @default.
- W4200583373 cites W2012034410 @default.
- W4200583373 cites W2012632997 @default.
- W4200583373 cites W2018661561 @default.
- W4200583373 cites W2033461775 @default.
- W4200583373 cites W2034383633 @default.
- W4200583373 cites W2034924547 @default.
- W4200583373 cites W2036897871 @default.
- W4200583373 cites W2037312364 @default.
- W4200583373 cites W2039953487 @default.
- W4200583373 cites W2050244960 @default.
- W4200583373 cites W2062407767 @default.
- W4200583373 cites W2068773707 @default.
- W4200583373 cites W2076188217 @default.
- W4200583373 cites W2081171890 @default.
- W4200583373 cites W2084514806 @default.
- W4200583373 cites W2084574772 @default.
- W4200583373 cites W2089756733 @default.
- W4200583373 cites W2094458603 @default.
- W4200583373 cites W2095316741 @default.
- W4200583373 cites W2096672118 @default.
- W4200583373 cites W2099085143 @default.
- W4200583373 cites W2102213696 @default.
- W4200583373 cites W2102853087 @default.
- W4200583373 cites W2103441770 @default.
- W4200583373 cites W2104127258 @default.
- W4200583373 cites W2104812418 @default.
- W4200583373 cites W2105057119 @default.
- W4200583373 cites W2105769855 @default.
- W4200583373 cites W2108917975 @default.
- W4200583373 cites W2116058267 @default.
- W4200583373 cites W2123507741 @default.
- W4200583373 cites W2136128927 @default.
- W4200583373 cites W2140538197 @default.
- W4200583373 cites W2146477392 @default.
- W4200583373 cites W2154315983 @default.
- W4200583373 cites W2157390509 @default.
- W4200583373 cites W2163605874 @default.
- W4200583373 cites W2168133698 @default.
- W4200583373 cites W2168744563 @default.
- W4200583373 cites W2170890869 @default.
- W4200583373 cites W2211315092 @default.
- W4200583373 cites W2256016639 @default.
- W4200583373 cites W2263875137 @default.
- W4200583373 cites W2266510186 @default.
- W4200583373 cites W2307091262 @default.
- W4200583373 cites W2402498701 @default.
- W4200583373 cites W2417483443 @default.
- W4200583373 cites W2418647706 @default.
- W4200583373 cites W2418824806 @default.
- W4200583373 cites W2611792444 @default.
- W4200583373 cites W2617784703 @default.
- W4200583373 cites W2782004981 @default.
- W4200583373 cites W2794260057 @default.
- W4200583373 cites W2803716386 @default.
- W4200583373 cites W2810196666 @default.
- W4200583373 cites W2841355558 @default.
- W4200583373 cites W2895424730 @default.
- W4200583373 cites W2896631860 @default.
- W4200583373 cites W2901335962 @default.
- W4200583373 cites W2910035054 @default.
- W4200583373 cites W2951912016 @default.
- W4200583373 cites W2972604213 @default.
- W4200583373 cites W3029661147 @default.
- W4200583373 cites W3152663054 @default.