Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to assess shared and distinct molecular changes in three mouse models commonly employed in preclinical CKD research and drug discovery. Methods: All experiments were conducted on male C57BL/6J mice. Mice underwent sham, unilateral ureter obstruction (UUO), or unilateral ischemic-reperfusion injury (uIRI) surgery and were terminated two- and 6-weeks post-surgery, respectively. The adenine-supplemented diet-induced (ADI) model of CKD was established by feeding with adenine diet for 6 weeks and compared to control diet feeding. For all models, endpoints included plasma biochemistry, kidney histology, and RNA sequencing. Results: All models displayed increased macrophage infiltration (F4/80 IHC) and fibrosis (collagen 1a1 IHC). Compared to corresponding controls, all models were characterized by an extensive number of renal differentially expressed genes (≥11,000), with a notable overlap in transcriptomic signatures across models. Gene expression markers of fibrosis, inflammation, and kidney injury supported histological findings. Interestingly, model-specific transcriptome signatures included several genes representing current drug targets for CKD, emphasizing advantages and limitations of the three CKD models in preclinical target and drug discovery. Conclusion: The UUO, uIRI, and ADI mouse models of CKD have significant commonalities in their renal global transcriptome profile. Model-specific renal transcriptional signatures should be considered when selecting the specific model in preclinical target and drug discovery.

1.
Stevens
PE
,
Levin
A
;
Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members
.
Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline
.
Ann Intern Med
.
2013
;
158
(
11
):
825
30
. .
2.
Ruiz-Ortega
M
,
Rayego-Mateos
S
,
Lamas
S
,
Ortiz
A
,
Rodrigues-Diez
RR
.
Targeting the progression of chronic kidney disease
.
Nat Rev Nephrol
.
2020
;
16
(
5
):
269
88
. .
3.
Kovesdy
CP
.
Epidemiology of chronic kidney disease: an update 2022
.
Kidney Int Suppl
.
2022
;
12
(
1
):
7
11
. .
4.
GBD 2019 Diseases and Injuries Collaborators
;
Abbas
KM
,
Abbasi-Kangevari
M
,
Abd-Allah
F
,
Abdelalim
A
,
Abdollahi
M
, et al
.
Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
.
Lancet
.
2020
;
396
(
10258
):
1204
22
. .
5.
Romagnani
P
,
Remuzzi
G
,
Glassock
R
,
Levin
A
,
Jager
KJ
,
Tonelli
M
, et al
.
Chronic kidney disease
.
Nat Rev Dis Prim
.
2017
;
3
:
17088
. .
6.
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators
;
Allen
C
,
Arora
M
,
Barber
RM
,
Brown
A
,
Carter
A
, et al
.
Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015
.
Lancet
.
2016
;
388
(
10053
):
1545
602
. .
7.
Kelly
JT
,
Su
G
,
Zhang
L
,
Qin
X
,
Marshall
S
,
González-Ortiz
A
, et al
.
Modifiable lifestyle factors for primary prevention of CKD: a systematic review and meta-analysis
.
J Am Soc Nephrol
.
2021
;
32
(
1
):
239
53
. .
8.
Xie
X
,
Liu
Y
,
Perkovic
V
,
Li
X
,
Ninomiya
T
,
Hou
W
, et al
.
Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a bayesian network meta-analysis of randomized clinical trials
.
Am J Kidney Dis
.
2016
;
67
(
5
):
728
41
. .
9.
Kidney KDIGO
.
Disease: improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease
.
Kidney Int Suppl
.
2013
;
3
:
1
150
.
10.
Perkovic
V
,
Jardine
MJ
,
Neal
B
,
Bompoint
S
,
Heerspink
HJL
,
Charytan
DM
, et al
.
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
.
N Engl J Med
.
2019
;
380
(
24
):
2295
306
. .
11.
Heerspink
HJL
,
Stefánsson
BV
,
Correa-Rotter
R
,
Chertow
GM
,
Greene
T
,
Hou
FF
, et al
.
Dapagliflozin in patients with chronic kidney disease
.
N Engl J Med
.
2020
;
383
(
15
):
1436
46
. .
12.
Hill
C
,
Spring
S
.
Empagliflozin and progression of kidney disease in type 2 diabetes
.
N Engl J Med
.
2016
;
375
(
18
):
1799
802
.
13.
Cannon
CP
,
Pratley
R
,
Dagogo-Jack
S
,
Mancuso
J
,
Huyck
S
,
Masiukiewicz
U
, et al
.
Cardiovascular outcomes with ertugliflozin in type 2 diabetes
.
N Engl J Med
.
2020
;
383
(
15
):
1425
35
. .
14.
The EMPA-KIDNEY Collaborative Group
,
Herrington
WG
,
Staplin
N
,
Wanner
C
,
Green
JB
,
Hauske
SJ
, et al
.
Empagliflozin in patients with chronic kidney disease
.
N Engl J Med
.
2023
;
388
(
2
):
117
27
. .
15.
Jafar
TH
.
FDA approval of dapagliflozin for chronic kidney disease: a remarkable achievement
.
Lancet
.
2021
;
398
(
10297
):
283
4
. .
16.
Frampton
JE
.
Finerenone: first approval
.
Drugs
.
2021
;
81
(
15
):
1787
94
. .
17.
Shiva
N
,
Sharma
N
,
Kulkarni
YA
,
Mulay
SR
,
Gaikwad
AB
.
Renal ischemia/reperfusion injury: an insight on in vitro and in vivo models
.
Life Sci
.
2020
;
256
:
117860
. .
18.
Martínez-Klimova
E
,
Aparicio-Trejo
OE
,
Tapia
E
,
Pedraza-Chaverri
J
.
Unilateral ureteral obstruction as a model to investigate fibrosis-attenuating treatments
.
Biomolecules
.
2019
;
9
(
4
):
141
. .
19.
Djudjaj
S
,
Boor
P
.
Cellular and molecular mechanisms of kidney fibrosis
.
Mol Aspects Med
.
2019
;
65
(
June
):
16
36
. .
20.
Berru
FN
,
Gray
SE
,
Thome
T
,
Kumar
RA
,
Salyers
ZR
,
Coleman
M
, et al
.
Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics
.
Sci Rep
.
2019
;
9
(
1
):
15547
15
. .
21.
Thome
T
,
Kumar
RA
,
Burke
SK
,
Khattri
RB
,
Salyers
ZR
,
Kelley
RC
, et al
.
Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease
.
JCI Insight
.
2020
;
6
(
1
):
e139826
. .
22.
Chevalier
RL
,
Forbes
MS
,
Thornhill
BA
.
Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy
.
Kidney Int
.
2009
;
75
(
11
):
1145
52
. .
23.
Coca
SG
,
Singanamala
S
,
Parikh
CR
.
Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis
.
Kidney Int
.
2012
;
81
(
5
):
442
8
. .
24.
Buvall
L
,
Menzies
RI
,
Williams
J
,
Woollard
KJ
,
Kumar
C
,
Granqvist
AB
, et al
.
Selecting the right therapeutic target for kidney disease
.
Front Pharmacol
.
2022
;
13
(
November
):
971065
5
. .
25.
Eddy
AA
,
López-Guisa
JM
,
Okamura
DM
,
Yamaguchi
I
.
Investigating mechanisms of chronic kidney disease in mouse models
.
Pediatr Nephrol
.
2012
;
27
(
8
):
1233
47
. .
26.
Jia
T
,
Olauson
H
,
Lindberg
K
,
Amin
R
,
Edvardsson
K
,
Lindholm
B
, et al
.
A novel model of adenine-induced tubulointerstitial nephropathy in mice
.
BMC Nephrol
.
2013
;
14
(
1
):
116
. .
27.
Rabe
M
,
Schaefer
F
.
Non-transgenic mouse models of kidney disease
.
Nephron
.
2016
;
133
(
1
):
53
61
. .
28.
Nogueira
A
,
Pires
MJ
,
Oliveira
PA
.
Pathophysiological mechanisms of renal fibrosis: a review of animal models and therapeutic strategies
.
Vivo
.
2017
;
31
(
1
):
1
22
. .
29.
Østergaard
MV
,
Sembach
FE
,
Skytte
JL
,
Roostalu
U
,
Secher
T
,
Overgaard
A
, et al
.
Automated image analyses of glomerular hypertrophy in a mouse model of diabetic nephropathy
.
Kidney360
.
2020
;
1
(
6
):
469
79
. .
30.
Sembach
FE
,
Fink
LN
,
Johansen
T
,
Boland
BB
,
Secher
T
,
Thrane
ST
, et al
.
Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice
.
Physiol Rep
.
2019
;
7
(
24
):
e14333
9
. .
31.
Dobin
A
,
Davis
CA
,
Schlesinger
F
,
Drenkow
J
,
Zaleski
C
,
Jha
S
, et al
.
STAR: ultrafast universal RNA-seq aligner
.
Bioinformatics
.
2013
;
29
(
1
):
15
21
. .
32.
Love
MI
,
Huber
W
,
Anders
S
.
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
.
Genome Biol
.
2014
;
15
(
12
):
550
21
. .
33.
Väremo
L
,
Nielsen
J
,
Nookaew
I
.
Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods
.
Nucleic Acids Res
.
2013
;
41
(
8
):
4378
91
. .
34.
Kolde
R
.
Pheatmap
.
2019
. Available from: https://cran.r-project.org/package=pheatmap.
35.
Gillespie
M
,
Jassal
B
,
Stephan
R
,
Milacic
M
,
Rothfels
K
,
Senff-Ribeiro
A
, et al
.
The reactome pathway knowledgebase 2022
.
Nucleic Acids Res
.
2022
;
50
(
D1
):
D687
92
. .
36.
Zhang
WR
,
Parikh
CR
.
Biomarkers of acute and chronic kidney disease
.
Annu Rev Physiol
.
2019
;
81
:
309
33
. .
37.
Mende
CW
.
Chronic kidney disease and SGLT2 inhibitors: a review of the evolving treatment landscape
.
Adv Ther
.
2022
;
39
(
1
):
148
64
. .
38.
Bulum
T
.
Nephroprotective properties of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists
.
Biomedicines
.
2022
;
10
(
10
):
2586
. .
39.
De Lorenzo
SB
,
Vrieze
AM
,
Johnson
RA
,
Lien
KR
,
Nath
KA
,
Garovic
VD
, et al
.
KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction
.
PLoS One
.
2022
;
17
(
4
):
e0266454
17
. .
40.
Li
H
,
Cai
H
,
Deng
J
,
Tu
X
,
Sun
Y
,
Huang
Z
, et al
.
TGF-β-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis
.
Biochim Biophys Acta Mol Basis Dis
.
2018
;
1864
(
2
):
520
32
. .
41.
Wei
L
,
Yu
Z
,
Liu
L
,
Zhou
Y
,
Bai
X
,
Wang
L
, et al
.
Integrated analysis of the CircRNA-based ceRNA network in renal fibrosis induced by ischemia reperfusion injury
.
Front Genet
.
2021
;
12
(
February
):
793182
14
. .
42.
Tamura
M
,
Aizawa
R
,
Hori
M
,
Ozaki
H
.
Progressive renal dysfunction and macrophage infiltration in interstitial fibrosis in an adenine-induced tubulointerstitial nephritis mouse model
.
Histochem Cell Biol
.
2009
;
131
(
4
):
483
90
. .
43.
Moonen
L
,
Geryl
H
,
D’Haese
PC
,
Vervaet
BA
.
Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury
.
BMC Nephrol
.
2018
;
19
(
1
):
343
12
. .
44.
Liu
J
,
Kumar
S
,
Dolzhenko
E
,
Alvarado
GF
,
Guo
J
,
Lu
C
, et al
.
Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion
.
JCI Insight
.
2017
;
2
(
18
):
e94716
18
. .
45.
Arvaniti
E
,
Moulos
P
,
Vakrakou
A
,
Chatziantoniou
C
,
Chadjichristos
C
,
Kavvadas
P
, et al
.
Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases
.
Sci Rep
.
2016
;
6
(
December 2015
):
26235
16
. .
46.
de Frutos
S
,
Luengo
A
,
García-Jérez
A
,
Hatem-Vaquero
M
,
Griera
M
,
O’Valle
F
, et al
.
Chronic kidney disease induced by an adenine rich diet upregulates integrin linked kinase (ILK) and its depletion prevents the disease progression
.
Biochim Biophys Acta Mol Basis Dis
.
2019
;
1865
(
6
):
1284
97
. .
47.
Loganathan
K
,
Said
ES
,
Winterrowd
E
,
Orebrand
M
,
He
L
,
Vanlandewijck
M
, et al
.
Angiopoietin-1 deficiency increases renal capillary rarefaction and tubulointerstitial fibrosis in mice
.
PLoS One
.
2018
;
13
(
1
):
1
18
.
48.
Chen
JH
,
Wu
CH
,
Jheng
JR
,
Chao
CT
,
Huang
JW
,
Hung
KY
,
Liu
SH
, et al
.
The down-regulation of XBP1, an unfolded protein response effector, promotes acute kidney injury to chronic kidney disease transition
.
J Biomed Sci
.
2022
;
29
(
1
):
46
22
. .
49.
Wang
B
,
Koh
P
,
Winbanks
C
,
Coughlan
MT
,
McClelland
A
,
Watson
A
, et al
.
miR-200a Prevents renal fibrogenesis through repression of TGF-β2 expression
.
Diabetes
.
2011
;
60
(
1
):
280
7
. .
50.
Yi
H
,
Huang
C
,
Shi
Y
,
Cao
Q
,
Chen
J
,
Chen
XM
, et al
.
Metformin attenuates renal fibrosis in a mouse model of adenine-induced renal injury through inhibiting TGF-β1 signaling pathways
.
Front Cell Dev Biol
.
2021
;
9
(
February
):
1
10
. .
51.
Yang
L
,
Besschetnova
TY
,
Brooks
CR
,
Shah
JV
,
Bonventre
JV
.
Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury
.
Nat Med
.
2010
;
16
(
5
):
535
143
. .
52.
Waasdorp
M
,
de Rooij
DM
,
Florquin
S
,
Duitman
JW
,
Spek
CA
.
Protease-activated receptor-1 contributes to renal injury and interstitial fibrosis during chronic obstructive nephropathy
.
J Cell Mol Med
.
2019
;
23
(
2
):
1268
79
. .
53.
Huang
A
,
Guo
G
,
Yu
Y
,
Yao
L
.
The roles of collagen in chronic kidney disease and vascular calcification
.
J Mol Med
.
2021
;
99
(
1
):
75
92
. .
54.
Chen
L
,
Yang
T
,
Lu
DW
,
Zhao
H
,
Feng
YL
,
Chen
H
, et al
.
Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment
.
Biomed Pharmacother
.
2018
;
101
:
670
81
. .
55.
Sánchez-Jaramillo
EA
,
Gasca-Lozano
LE
,
Vera-Cruz
JM
,
Hernández-Ortega
LD
,
Gurrola-Díaz
CM
,
Bastidas-Ramírez
BE
, et al
.
Nanoparticles formulation improves the antifibrogenic effect of quercetin on an adenine-induced model of chronic kidney disease
.
Int J Mol Sci
.
2022
;
23
(
10
):
5392
17
. .
56.
Bai
Y
,
Wang
W
,
Yin
P
,
Gao
J
,
Na
L
,
Sun
Y
, et al
.
Ruxolitinib alleviates renal interstitial fibrosis in UUO mice
.
Int J Biol Sci
.
2020
;
16
(
2
):
194
203
. .
57.
Li
C
,
Shen
Y
,
Huang
L
,
Liu
C
,
Wang
J
.
Senolytic therapy ameliorates renal fibrosis postacute kidney injury by alleviating renal senescence
.
FASEB J
.
2021
;
35
(
1
):
e21229
16
. .
58.
Akhurst
RJ
.
Targeting TGF-β signaling for therapeutic gain
.
Cold Spring Harb Perspect Biol
.
2017
;
9
(
10
):
a022301
30
. .
59.
Shi
N
,
Wang
Z
,
Zhu
H
,
Liu
W
,
Zhao
M
,
Jiang
X
, et al
.
Research progress on drugs targeting the TGF-β signaling pathway in fibrotic diseases
.
Immunol Res
.
2022
;
70
(
3
):
276
88
. .
60.
Wang
SN
,
Lapage
J
,
Hirschberg
R
.
Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy
.
J Am Soc Nephrol
.
2001
;
12
(
11
):
2392
9
. .
61.
Tang
J
,
Liu
N
,
Zhuang
S
.
Role of epidermal growth factor receptor in acute and chronic kidney injury
.
Kidney Int
.
2013
;
83
(
5
):
804
10
. .
62.
Li
Z
,
Zhou
L
,
Wang
Y
,
Miao
J
,
Hong
X
,
Hou
FF
, et al
.
(Pro)renin receptor is an amplifier of wnt/β-catenin signaling in kidney injury and fibrosis
.
J Am Soc Nephrol
.
2017
;
28
(
8
):
2393
408
. .
63.
Peng
X
,
Xiao
Z
,
Zhang
J
,
Li
Y
,
Dong
Y
,
Du
J
.
IL-17A produced by both γδ T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction
.
J Pathol
.
2015
;
235
(
1
):
79
89
. .
64.
Peralta
CA
,
Katz
R
,
Bonventre
JV
,
Sabbisetti
V
,
Siscovick
D
,
Sarnak
M
, et al
.
Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the multi-ethnic study of atherosclerosis (MESA)
.
Am J Kidney Dis
.
2012
;
60
(
6
):
904
11
. .
65.
Amdur
RL
,
Feldman
HI
,
Gupta
J
,
Yang
W
,
Kanetsky
P
,
Shlipak
M
, et al
.
Inflammation and progression of CKD: the CRIC study
.
Clin J Am Soc Nephrol
.
2016
;
11
(
9
):
1546
56
. .
66.
Eardley
KS
,
Zehnder
D
,
Quinkler
M
,
Lepenies
J
,
Bates
RL
,
Savage
CO
, et al
.
The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease
.
Kidney Int
.
2006
;
69
(
7
):
1189
97
. .
67.
Pawlak
K
,
Kowalewska
A
,
Mysliwiec
M
,
Pawlak
D
.
3-hydroxyanthranilic acid is independently associated with monocyte chemoattractant protein-1 (CCL2) and macrophage inflammatory protein-1beta (CCL4) in patients with chronic kidney disease
.
Clin Biochem
.
2010
;
43
(
13–14
):
1101
6
. .
68.
Aguiar
CF
,
Naffah-de-Souza
C
,
Castoldi
A
,
Corrêa-Costa
M
,
Braga
TT
,
Naka
ÉL
, et al
.
Administration of α-galactosylceramide improves adenine-induced renal injury
.
Mol Med
.
2015
;
21
(
1
):
553
62
. .
69.
Midgley
AC
,
Wei
Y
,
Zhu
D
,
Gao
F
,
Yan
H
,
Khalique
A
, et al
.
Multifunctional natural polymer nanoparticles as antifibrotic gene carriers for CKD therapy
.
J Am Soc Nephrol
.
2020
;
31
(
10
):
2292
311
. .
70.
Black
LM
,
Lever
JM
,
Traylor
AM
,
Chen
B
,
Yang
Z
,
Esman
SK
, et al
.
Divergent effects of AKI to CKD models on inflammation and fibrosis
.
Am J Physiol Physiol
.
2018
;
315
(
4
):
F1107
18
. .
71.
Brus
JE
,
Quan
DL
,
Wiley
KJ
,
Browning
B
,
Ter Haar
H
,
Lutz
R
, et al
.
Diet significantly influences the immunopathology and severity of kidney injury in male C57Bl/6J mice in a model dependent manner
.
Nutrients
.
2021
;
13
(
5
):
1521
. .
72.
Cuadros
T
,
Trilla
E
,
Sarró
E
,
Vilà
MR
,
Vilardell
J
,
de Torres
I
, et al
.
HAVCR/KIM-1 activates the IL-6/STAT-3 pathway in clear cell renal cell carcinoma and determines tumor progression and patient outcome
.
Cancer Res
.
2014
;
74
(
5
):
1416
28
. .
73.
Viau
A
,
El Karoui
K
,
Laouari
D
,
Burtin
M
,
Nguyen
C
,
Mori
K
, et al
.
Lipocalin 2 is essential for chronic kidney disease progression in mice and humans
.
J Clin Invest
.
2010
;
120
(
11
):
4065
76
. .
74.
Kaleta
B
.
The role of osteopontin in kidney diseases
.
Inflamm Res
.
2019
;
68
(
2
):
93
102
. .
75.
Su
H
,
Lei
CT
,
Zhang
C
.
Interleukin-6 signaling pathway and its role in kidney disease: an update
.
Front Immunol
.
2017
;
8
:
405
10
. .
76.
Nakagawa
S
,
Nishihara
K
,
Miyata
H
,
Shinke
H
,
Tomita
E
,
Kajiwara
M
, et al
.
Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease
.
PLoS One
.
2015
;
10
(
8
):
e0136994
14
. .
77.
Lorenzen
J
,
Krämer
R
,
Kliem
V
,
Bode-Boeger
SM
,
Veldink
H
,
Haller
H
, et al
.
Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease
.
Eur J Clin Invest
.
2010
;
40
(
4
):
294
300
. .
78.
Fabian
SL
,
Penchev
RR
,
St-Jacques
B
,
Rao
AN
,
Sipilä
P
,
West
KA
, et al
.
Hedgehog-Gli pathway activation during kidney fibrosis
.
Am J Pathol
.
2012
;
180
(
4
):
1441
53
. .
79.
Liu
X
,
Miao
J
,
Wang
C
,
Zhou
S
,
Chen
S
,
Ren
Q
, et al
.
Tubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis
.
Kidney Int
.
2020
;
97
(
6
):
1181
95
. .
80.
Kramann
R
,
Fleig
SV
,
Schneider
RK
,
Fabian
SL
,
DiRocco
DP
,
Maarouf
O
, et al
.
Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis
.
J Clin Invest
.
2015
;
125
(
8
):
2935
51
. .
81.
Di Marco
GS
,
Kentrup
D
,
Reuter
S
,
Mayer
AB
,
Golle
L
,
Tiemann
K
, et al
.
Soluble Flt-1 links microvascular disease with heart failure in CKD
.
Basic Res Cardiol
.
2015
;
110
(
3
):
30
. .
82.
Neder
TH
,
Schrankl
J
,
Fuchs
MAA
,
Broeker
KAE
,
Wagner
C
.
Endothelin receptors in renal interstitial cells do not contribute to the development of fibrosis during experimental kidney disease
.
Pflugers Arch
.
2021
;
473
(
10
):
1667
83
. .
83.
Feng
Y
,
Ren
J
,
Gui
Y
,
Wei
W
,
Shu
B
,
Lu
Q
, et al
.
Wnt/β-Catenin–Promoted macrophage alternative activation contributes to kidney fibrosis
.
J Am Soc Nephrol
.
2018
;
29
(
1
):
182
93
. .
84.
Chaabane
W
,
Praddaude
F
,
Buleon
M
,
Jaafar
A
,
Vallet
M
,
Rischmann
P
, et al
.
Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO)
.
Am J Physiol Ren Physiol
.
2013
;
304
(
4
):
432
9
. .
85.
Nangaku
M
,
Kitching
AR
,
Boor
P
,
Fornoni
A
,
Floege
J
,
Coates
PT
, et al
.
International Society of Nephrology first consensus guidance for preclinical animal studies in translational nephrology
.
Kidney Int
.
2023
;
104
(
1
):
36
45
. .
You do not currently have access to this content.