DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants.

ABSTRACT:

Background

Two variants in the gene encoding apolipoprotein L1 (APOL1) that are highly associated with African ancestry are major contributors to the large racial disparity in rates of human kidney disease. We previously demonstrated that recruitment of APOL1 risk variants G1 and G2 from the endoplasmic reticulum to lipid droplets leads to reduced APOL1-mediated cytotoxicity in human podocytes.

Methods

We used CRISPR-Cas9 gene editing of induced pluripotent stem cells to develop human-derived APOL1^G0/G0 and APOL1^G2/G2 kidney organoids on an isogenic background, and performed bulk RNA sequencing of organoids before and after treatment with IFN-γ. We examined the number and distribution of lipid droplets in response to treatment with inhibitors of

SUBMITTER: Chun J 

PROVIDER: S-EPMC9063887 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature