A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.
focal segmental glomerular sclerosis
gene expression
glomerulus
mitochondria
nephrotic syndrome
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
14
02
2021
revised:
20
10
2021
accepted:
29
10
2021
pubmed:
21
12
2021
medline:
28
6
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34929253
pii: S0085-2538(21)01149-2
doi: 10.1016/j.kint.2021.10.041
pmc: PMC9206042
mid: NIHMS1786692
pii:
doi:
Substances chimiques
APOL1 protein, human
0
Apolipoprotein L1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
136-148Subventions
Organisme : NIDDK NIH HHS
ID : RC2 DK122397
Pays : United States
Organisme : NIDDK NIH HHS
ID : UM1 DK105554
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK083912
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD007092
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119380
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108805
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG011453
Pays : United States
Investigateurs
K Dell
(K)
J Sedor
(J)
M Schachere
(M)
J Negrey
(J)
K Lemley
(K)
B Silesky
(B)
T Srivastava
(T)
A Garrett
(A)
C Sethna
(C)
K Laurent
(K)
P Canetta
(P)
A Pradhan
(A)
L Greenbaum
(L)
C Wang
(C)
C Kang
(C)
S Adler
(S)
J LaPage
(J)
A Athavale
(A)
M Itteera
(M)
M Atkinson
(M)
T Dell
(T)
F Fervenza
(F)
M Hogan
(M)
J Lieske
(J)
V Chernitskiy
(V)
F Kaskel
(F)
M Ross
(M)
P Flynn
(P)
J Kopp
(J)
J Blake
(J)
H Trachtman
(H)
O Zhdanova
(O)
F Modersitzki
(F)
S Vento
(S)
R Lafayette
(R)
K Mehta
(K)
C Gadegbeku
(C)
S Quinn-Boyle
(S)
M Hladunewich
(M)
H Reich
(H)
P Ling
(P)
M Romano
(M)
A Fornoni
(A)
C Bidot
(C)
M Kretzler
(M)
D Gipson
(D)
A Williams
(A)
C Klida
(C)
V Derebail
(V)
K Gibson
(K)
E Cole
(E)
J Ormond-Foster
(J)
L Holzman
(L)
K Meyers
(K)
K Kallem
(K)
A Swenson
(A)
K Sambandam
(K)
Z Wang
(Z)
M Rogers
(M)
A Jefferson
(A)
S Hingorani
(S)
K Tuttle
(K)
M Bray
(M)
E Pao
(E)
A Cooper
(A)
J J Lin
(JJ)
Stefanie Baker
(S)
M Kretzler
(M)
L Barisoni
(L)
J Bixler
(J)
H Desmond
(H)
S Eddy
(S)
D Fermin
(D)
C Gadegbeku
(C)
B Gillespie
(B)
D Gipson
(D)
L Holzman
(L)
V Kurtz
(V)
M Larkina
(M)
S Li
(S)
S Li
(S)
C C Lienczewski
(CC)
J Liu
(J)
T Mainieri
(T)
L Mariani
(L)
M Sampson
(M)
J Sedor
(J)
A Smith
(A)
A Williams
(A)
J Zee
(J)
Carmen Avila-Casado
(C)
Serena Bagnasco
(S)
Joseph Gaut
(J)
Stephen Hewitt
(S)
Jeff Hodgin
(J)
Kevin Lemley
(K)
Laura Mariani
(L)
Matthew Palmer
(M)
Avi Rosenberg
(A)
Virginie Royal
(V)
David Thomas
(D)
Jarcy Zee
(J)
Laura Barisoni
(L)
Cynthia Nast
(C)
K Dell
(K)
J Sedor
(J)
M Schachere
(M)
J Negrey
(J)
K Lemley
(K)
B Silesky
(B)
T Srivastava
(T)
A Garrett
(A)
C Sethna
(C)
K Laurent
(K)
P Canetta
(P)
A Pradhan
(A)
L Greenbaum
(L)
C Wang
(C)
C Kang
(C)
S Adler
(S)
J LaPage
(J)
A Athavale
(A)
M Itteera
(M)
M Atkinson
(M)
T Dell
(T)
F Fervenza
(F)
M Hogan
(M)
J Lieske
(J)
V Chernitskiy
(V)
F Kaskel
(F)
M Ross
(M)
P Flynn
(P)
J Kopp
(J)
J Blake
(J)
H Trachtman
(H)
O Zhdanova
(O)
F Modersitzki
(F)
S Vento
(S)
R Lafayette
(R)
K Mehta
(K)
C Gadegbeku
(C)
S Quinn-Boyle
(S)
M Hladunewich
(M)
H Reich
(H)
P Ling
(P)
M Romano
(M)
A Fornoni
(A)
C Bidot
(C)
M Kretzler
(M)
D Gipson
(D)
A Williams
(A)
C Klida
(C)
V Derebail
(V)
K Gibson
(K)
E Cole
(E)
J Ormond-Foster
(J)
L Holzman
(L)
K Meyers
(K)
K Kallem
(K)
A Swenson
(A)
K Sambandam
(K)
Z Wang
(Z)
M Rogers
(M)
A Jefferson
(A)
S Hingorani
(S)
K Tuttle
(K)
M Bray
(M)
E Pao
(E)
A Cooper
(A)
J J Lin
(JJ)
Stefanie Baker
(S)
M Kretzler
(M)
L Barisoni
(L)
J Bixler
(J)
H Desmond
(H)
S Eddy
(S)
D Fermin
(D)
C Gadegbeku
(C)
B Gillespie
(B)
D Gipson
(D)
L Holzman
(L)
V Kurtz
(V)
M Larkina
(M)
S Li
(S)
S Li
(S)
C C Lienczewski
(CC)
J Liu
(J)
T Mainieri
(T)
L Mariani
(L)
M Sampson
(M)
J Sedor
(J)
A Smith
(A)
A Williams
(A)
J Zee
(J)
Carmen Avila-Casado
(C)
Serena Bagnasco
(S)
Joseph Gaut
(J)
Stephen Hewitt
(S)
Jeff Hodgin
(J)
Kevin Lemley
(K)
Laura Mariani
(L)
Matthew Palmer
(M)
Avi Rosenberg
(A)
Virginie Royal
(V)
David Thomas
(D)
Jarcy Zee
(J)
Laura Barisoni
(L)
Cynthia Nast
(C)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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