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A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.

Publication ,  Journal Article
McNulty, MT; Fermin, D; Eichinger, F; Jang, D; Kretzler, M; Burtt, NP; Pollak, MR; Flannick, J; Weins, A; Friedman, DJ; Sampson, MG ...
Published in: Kidney Int
July 2022

Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1's pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.

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Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

July 2022

Volume

102

Issue

1

Start / End Page

136 / 148

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transcriptome
  • Kidney Glomerulus
  • Humans
  • HEK293 Cells
  • Glomerulosclerosis, Focal Segmental
  • Apolipoprotein L1
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McNulty, M. T., Fermin, D., Eichinger, F., Jang, D., Kretzler, M., Burtt, N. P., … Sampson, M. G. (2022). A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis. Kidney Int, 102(1), 136–148. https://doi.org/10.1016/j.kint.2021.10.041
McNulty, Michelle T., Damian Fermin, Felix Eichinger, Dongkeun Jang, Matthias Kretzler, Noël P. Burtt, Martin R. Pollak, et al. “A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.Kidney Int 102, no. 1 (July 2022): 136–48. https://doi.org/10.1016/j.kint.2021.10.041.
McNulty MT, Fermin D, Eichinger F, Jang D, Kretzler M, Burtt NP, et al. A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis. Kidney Int. 2022 Jul;102(1):136–48.
McNulty, Michelle T., et al. “A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.Kidney Int, vol. 102, no. 1, July 2022, pp. 136–48. Pubmed, doi:10.1016/j.kint.2021.10.041.
McNulty MT, Fermin D, Eichinger F, Jang D, Kretzler M, Burtt NP, Pollak MR, Flannick J, Weins A, Friedman DJ, Nephrotic Syndrome Study Network (NEPTUNE), Sampson MG. A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis. Kidney Int. 2022 Jul;102(1):136–148.
Journal cover image

Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

July 2022

Volume

102

Issue

1

Start / End Page

136 / 148

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transcriptome
  • Kidney Glomerulus
  • Humans
  • HEK293 Cells
  • Glomerulosclerosis, Focal Segmental
  • Apolipoprotein L1
  • 3202 Clinical sciences
  • 1103 Clinical Sciences