Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria
Pflügers Archiv - European Journal of Physiology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 18, 2025
Language: Английский
Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet
Arteriosclerosis Thrombosis and Vascular Biology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 21, 2024
BACKGROUND:
Pharmacological
inhibition
of
megalin
(also
known
as
LRP2
[low-density
lipoprotein
receptor-related
protein-2])
attenuates
atherosclerosis
in
hypercholesterolemic
mice.
Since
is
abundant
renal
proximal
tubule
cells
(PTCs),
the
purpose
this
study
was
to
determine
whether
PTC-specific
deletion
reduces
hypercholesterolemia-induced
METHODS:
Female
Lrp2
f/f
mice
were
bred
with
male
Ndrg1
-
Cre
ERT2
+/0
develop
PTC-LRP2
+/+
and
−/−
littermates.
To
atherosclerosis,
all
an
LDL
(low-density
lipoprotein)
receptor
background
fed
a
Western
diet
induce
atherosclerosis.
RESULTS:
did
not
attenuate
either
sex.
Serendipitously,
we
discovered
that
led
interstitial
infiltration
CD68+
tubular
atrophy.
The
pathology
only
evident
but
normal
laboratory
diet.
Renal
pathologies
also
observed
same
diet,
demonstrating
dependent
on
hypercholesterolemia.
In
contrast,
female
had
no
apparent
pathologies.
vivo
multiphoton
microscopy
demonstrated
dramatically
diminished
ALB
(albumin)
accumulation
PTCs
within
10
days
feeding.
RNA-sequencing
analyses
upregulation
inflammation-related
pathways
kidney.
CONCLUSIONS:
does
affect
leads
tubulointerstitial
nephritis
severe
Language: Английский
Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 15, 2024
ABSTRACT
Background
Pharmacological
inhibition
of
megalin
(also
known
as
low-density
lipoprotein
receptor-related
protein
2:
LRP2)
attenuates
atherosclerosis
in
hypercholesterolemic
mice.
Since
is
abundant
renal
proximal
tubule
cells
(PTCs),
the
purpose
this
study
was
to
determine
whether
PTC-specific
deletion
reduces
hypercholesterolemia-induced
Methods
Female
Lrp2
f/f
mice
were
bred
with
male
Ndrg1
-
Cre
ERT2
+/0
develop
PTC-LRP2
+/+
and
−/−
littermates.
To
atherosclerosis,
all
an
LDL
receptor
background
fed
a
Western
diet
induce
atherosclerosis.
Results
did
not
attenuate
either
sex.
Serendipitously,
we
discovered
that
led
interstitial
infiltration
CD68+
tubular
atrophy.
The
pathology
only
evident
diet,
but
normal
laboratory
diet.
Renal
pathologies
also
observed
same
demonstrating
dependent
on
hypercholesterolemia.
In
contrast,
female
had
no
apparent
pathologies.
vivo
multiphoton
microscopy
demonstrated
dramatically
diminished
albumin
accumulation
PTCs
within
10
days
feeding.
RNA
sequencing
analyses
upregulation
inflammation-related
pathways
kidney.
Conclusions
does
affect
leads
tubulointerstitial
nephritis
severe
Language: Английский
Megalin as a Metabolic Modulator in the Kidney and Beyond
Function,
Journal Year:
2024,
Volume and Issue:
5(5)
Published: Jan. 1, 2024
Language: Английский
Solitary Kidney Seeks Potassium Alkali to Lower the Pressure
Journal of the American Society of Nephrology,
Journal Year:
2024,
Volume and Issue:
35(10), P. 1300 - 1302
Published: Aug. 21, 2024
1Renal-Electrolyte
Division,
Department
of
Medicine,
University
Pittsburgh
School
Pittsburgh,
Pennsylvania
2Pittsburgh
Center
for
Kidney
Research,
3Division
Nephrology
and
Hypertension,
Internal
Utah
Spencer
Fox
Eccles
Salt
Lake
City,
4Molecular
Medicine
Program,
5Department
Human
Genetics,
6Medical
Service,
Veterans
Affairs
City
Health
Care
System,
Correspondence:
Dr.
Aylin
R.
Rodan,
email:
[email
protected]
See
related
article,
"Potassium-Alkali–Enriched
Diet,
Proteinuria
following
Uninephrectomy,"
on
pages
XXX–XXX.
Language: Английский