Kisspeptin-10 Prevents the Development of Cerebral Aneurysms by Reducing the Expression of Egr-1.

Yu H, Xie M, Liufu X, Xu Y, Chen L

CNS neuroscience & therapeutics1 May 2025Cited by 3 (Europe PMC)

PMID40384564PMCIDPMC12086517DOI10.1111/cns.70413PepBankPUB-40384564

Summary

AimsCerebral aneurysms (CAs) are a prevalent brain condition with poorly understood pathological features. The Kisspeptin-10 (KP-10)/G protein-coupled receptor 54 (GPR54) system is a vital neuroendocrine pathway primarily implicated in the regulation of reproductive functions and energy metabolism. This research explores the role of the KP-10/GPR54 system in CAs.Materials and methodsSerum levels of KP-10 in CA patients and animal models were assessed using commercial ELISA kits. Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10. The CA profiles were evaluated using Verhoeff-van Gieson staining. Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM). Angiogenic tube formation was then assessed.ResultsWe found that KP-10 levels were reduced in both CA patients and mouse models. In CA mice, Gpr54 expression in the Circle of Willis (COW) was also decreased. KP-10 reduced CA size in wild-type mice, but not in Gpr54 knockout mice. It also reduced matrix metalloproteinase-9 (MMP-9), macrophage infiltration, and vascular endothelial growth factor-A (VEGF-A) expression, effects that were absent in Gpr54 knockout mice. In vitro, KP-10 inhibited Ang II-induced proliferation, angiogenic tube formation, and VEGF-A expression in HBMVECs by reducing early growth response-1 (Egr-1). These effects were abolished when Gpr54 was knocked down, indicating that KP-10's action is dependent on Gpr54.ConclusionThis study shows that KP-10 binding to Gpr54 inhibits Egr-1 expression, thereby suppressing MMP-9 and VEGF-A, reducing macrophage infiltration and angiogenesis, and preventing cerebral aneurysm development. Thus, the KP-10/Gpr54 system is a key therapeutic target for the treatment of cerebral aneurysms.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

10 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In wild-type mice with cerebral aneurysms, KP-10 reduced aneurysm size.
In plain wordsIn mice with cerebral aneurysms, KP-10 made the aneurysms smaller.
Peptide
Kisspeptin-10
Outcome
DecreaseCerebral aneurysm size in wild-type mice
Study
mousen: not reported in source
cerebral aneurysm mouse model
Comparator
Untreated cerebral aneurysm mice
Outcome group
Endogenous peptide levels · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
KP-10 reduced CA size in wild-type mice, but not in Gpr54 knockout mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10.
Show in the study text Report a problemFND-4038456404
02AnimalAnimal study (in vivo)Efficacy outcome
In Gpr54 knockout mice with cerebral aneurysms, KP-10 did not reduce aneurysm size.
In plain wordsIn mice lacking the KP-10 receptor, KP-10 did not make aneurysms smaller.
Peptide
Kisspeptin-10
Outcome
No significant changeCerebral aneurysm size in Gpr54 knockout mice
Study
mousen: not reported in source
cerebral aneurysm in Gpr54 knockout mice
Comparator
Untreated Gpr54 knockout mice with aneurysm
Outcome group
Endogenous peptide levels · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
KP-10 reduced CA size in wild-type mice, but not in Gpr54 knockout mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10.
Show in the study text Report a problemFND-4038456405
03AnimalAnimal study (in vivo)Mechanism
In mice with cerebral aneurysms, KP-10 reduced matrix metalloproteinase-9 (MMP-9); the effect was absent in Gpr54 knockout mice.
In plain wordsIn mice with cerebral aneurysms, KP-10 lowered the tissue-damaging enzyme MMP-9.
Peptide
Kisspeptin-10
Outcome
DecreaseMMP-9
Study
mousen: not reported in source
cerebral aneurysm mouse model
Comparator
Untreated cerebral aneurysm mice
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
It also reduced matrix metalloproteinase-9 (MMP-9), macrophage infiltration, and vascular endothelial growth factor-A (VEGF-A) expression, effects that were absent in Gpr54 knockout mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10.
Show in the study text Report a problemFND-4038456406
04AnimalAnimal study (in vivo)Mechanism
In mice with cerebral aneurysms, KP-10 reduced macrophage infiltration; the effect was absent in Gpr54 knockout mice.
In plain wordsIn mice with cerebral aneurysms, KP-10 reduced the number of immune cells entering the vessel wall.
Peptide
Kisspeptin-10
Outcome
DecreaseMacrophage infiltration
Study
mousen: not reported in source
cerebral aneurysm mouse model
Comparator
Untreated cerebral aneurysm mice
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
It also reduced matrix metalloproteinase-9 (MMP-9), macrophage infiltration, and vascular endothelial growth factor-A (VEGF-A) expression, effects that were absent in Gpr54 knockout mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10.
Show in the study text Report a problemFND-4038456407
05AnimalAnimal study (in vivo)Mechanism
In mice with cerebral aneurysms, KP-10 reduced vascular endothelial growth factor-A (VEGF-A) expression; the effect was absent in Gpr54 knockout mice.
In plain wordsIn mice with cerebral aneurysms, KP-10 lowered the blood-vessel growth factor VEGF-A.
Peptide
Kisspeptin-10
Outcome
DecreaseVEGF-A expression
Study
mousen: not reported in source
cerebral aneurysm mouse model
Comparator
Untreated cerebral aneurysm mice
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
It also reduced matrix metalloproteinase-9 (MMP-9), macrophage infiltration, and vascular endothelial growth factor-A (VEGF-A) expression, effects that were absent in Gpr54 knockout mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were divided into five groups: WT, GPR54^-/-, CA, CA + KP-10, and CA + GPR54^-/- + KP-10.
Show in the study text Report a problemFND-4038456408
06LabIn vitro (cells)Efficacy outcome
In human brain microvascular endothelial cells, KP-10 inhibited Ang II-induced proliferation.
In plain wordsIn lab cells from human brain vessels, KP-10 reduced the cell growth that Ang II causes.
Peptide
Kisspeptin-10
Outcome
DecreaseAng II-induced proliferation
Study
humann: not reported in source
human brain microvascular endothelial cells (HBMVECs) stimulated with Ang II
Comparator
Ang II alone
Outcome group
Endogenous peptide levels · Cardiovascular
Studied dose
50 and 100 nMAs given in this study (human).
Source sentences
Summary
In vitro, KP-10 inhibited Ang II-induced proliferation, angiogenic tube formation, and VEGF-A expression in HBMVECs by reducing early growth response-1 (Egr-1).
1 context sentence(design, population, supporting numbers)
Summary · context
Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM).
Show in the study text Report a problemFND-4038456409
07LabIn vitro (cells)Efficacy outcome
In human brain microvascular endothelial cells, KP-10 inhibited Ang II-induced angiogenic tube formation.
In plain wordsIn lab cells from human brain vessels, KP-10 reduced the new vessel-like tubes that Ang II causes.
Peptide
Kisspeptin-10
Outcome
DecreaseAng II-induced angiogenic tube formation
Study
humann: not reported in source
human brain microvascular endothelial cells (HBMVECs) stimulated with Ang II
Comparator
Ang II alone
Outcome group
Endogenous peptide levels · Cardiovascular
Studied dose
50 and 100 nMAs given in this study (human).
Source sentences
Summary
In vitro, KP-10 inhibited Ang II-induced proliferation, angiogenic tube formation, and VEGF-A expression in HBMVECs by reducing early growth response-1 (Egr-1).
1 context sentence(design, population, supporting numbers)
Summary · context
Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM).
Show in the study text Report a problemFND-4038456410
08LabIn vitro (cells)Mechanism
In human brain microvascular endothelial cells, KP-10 inhibited Ang II-induced VEGF-A expression.
In plain wordsIn lab cells from human brain vessels, KP-10 lowered the growth factor VEGF-A that Ang II raises.
Peptide
Kisspeptin-10
Outcome
DecreaseAng II-induced VEGF-A expression
Study
humann: not reported in source
human brain microvascular endothelial cells (HBMVECs) stimulated with Ang II
Comparator
Ang II alone
Outcome group
Endogenous peptide levels · Cardiovascular
Studied dose
50 and 100 nMAs given in this study (human).
Source sentences
Summary
In vitro, KP-10 inhibited Ang II-induced proliferation, angiogenic tube formation, and VEGF-A expression in HBMVECs by reducing early growth response-1 (Egr-1).
1 context sentence(design, population, supporting numbers)
Summary · context
Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM).
Show in the study text Report a problemFND-4038456411
09LabIn vitro (cells)Mechanism
In human brain microvascular endothelial cells, KP-10 acted by reducing early growth response-1 (Egr-1).
In plain wordsIn lab cells from human brain vessels, KP-10 lowered the gene regulator Egr-1.
Peptide
Kisspeptin-10
Outcome
DecreaseEgr-1 expression
Study
humann: not reported in source
human brain microvascular endothelial cells (HBMVECs) stimulated with Ang II
Comparator
Ang II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
50 and 100 nMAs given in this study (human).
Source sentences
Summary
by reducing early growth response-1 (Egr-1).
1 context sentence(design, population, supporting numbers)
Summary · context
Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM).
Show in the study text Report a problemFND-4038456412
10LabIn vitro (cells)Mechanism
In human brain microvascular endothelial cells, knockdown of Gpr54 abolished the effects of KP-10.
In plain wordsIn lab cells, removing the KP-10 receptor Gpr54 cancelled the effects of KP-10.
Peptide
Kisspeptin-10
Outcome
Not applicableKP-10 effects after Gpr54 knockdown
Study
humann: not reported in source
HBMVECs with Gpr54 knockdown
Comparator
KP-10 without Gpr54 knockdown
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
50 and 100 nMAs given in this study (human).
Source sentences
Summary
These effects were abolished when Gpr54 was knocked down, indicating that KP-10's action is dependent on Gpr54.
1 context sentence(design, population, supporting numbers)
Summary · context
Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10^-7 mol/L) with or without KP-10 (50, 100 nM).
Show in the study text Report a problemFND-4038456413

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

11HumanEndogenous levelObservational studyOther
Serum levels of the body's own KP-10 were reduced in patients with cerebral aneurysms.
In plain wordsPeople with cerebral aneurysms had lower levels of the body's own KP-10 in blood.
Peptide
Kisspeptin-10
Outcome
DecreaseSerum KP-10 level in cerebral aneurysm patients
Study
n: not reported in source
Outcome group
Endogenous peptide levels · Cardiovascular
Source sentences
Summary
We found that KP-10 levels were reduced in both CA patients and mouse models.
1 context sentence(design, population, supporting numbers)
Summary · context
Serum levels of KP-10 in CA patients and animal models were assessed using commercial ELISA kits.
This result measures the body's own Kisspeptin-10. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4038456401
12AnimalEndogenous levelAnimal study (in vivo)Other
Serum levels of the body's own KP-10 were reduced in mouse models of cerebral aneurysm.
In plain wordsIn mice with cerebral aneurysms, the body's own KP-10 levels in blood were lower.
Peptide
Kisspeptin-10
Outcome
DecreaseSerum KP-10 level in cerebral aneurysm mice
Study
mousen: not reported in source
cerebral aneurysm mouse model
Outcome group
Endogenous peptide levels · Cardiovascular
Source sentences
Summary
We found that KP-10 levels were reduced in both CA patients and mouse models.
1 context sentence(design, population, supporting numbers)
Summary · context
Serum levels of KP-10 in CA patients and animal models were assessed using commercial ELISA kits.
This result measures the body's own Kisspeptin-10. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4038456402

Studies that did not test the peptide alone1

In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Kisspeptin-10.

13AnimalNot a test of Kisspeptin-10 aloneAnimal study (in vivo)Other
Expression of Gpr54, the KP-10 receptor, in the Circle of Willis was decreased in cerebral aneurysm mice.
In plain wordsIn mice with cerebral aneurysms, the receptor for the body's own KP-10 was lower in a key brain artery ring.
Peptide
Kisspeptin-10
Outcome
DecreaseGpr54 expression in Circle of Willis
Study
mousen: not reported in source
cerebral aneurysm mouse model
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
In CA mice, Gpr54 expression in the Circle of Willis (COW) was also decreased.
1 context sentence(design, population, supporting numbers)
Summary · context
The Kisspeptin-10 (KP-10)/G protein-coupled receptor 54 (GPR54) system is a vital neuroendocrine pathway primarily implicated in the regulation of reproductive functions and energy metabolism.
In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Kisspeptin-10.
Show in the study text Report a problemFND-4038456403

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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