Kisspeptin-54 confers renal protection in diabetic nephropathy by ameliorating endothelial permeability through ZEB1 inhibition.

Gao L, Lv Q, Wang Y, Zhang D, Ding W, Cao L, Ou S

Tissue & cell27 Mar 2026

PMID41950743DOI10.1016/j.tice.2026.103503PepBankPUB-41950743

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study9

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

01AnimalAnimal study (in vivo)Efficacy outcome
In db/db mice, Kisspeptin‑54 treatment restored the junction protein ZO-1.
In plain wordsIn diabetic mice, Kisspeptin‑54 restored a protein that holds kidney barrier cells together.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseJunction protein ZO-1
Study
mousen: not reported in source
db/db mice (type 2 diabetic nephropathy model)
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Kisspeptin-54 treatment in mice restored the junction protein ZO-1, reduced albuminuria and serum creatinine.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
Report a problemFND-4195074302
02AnimalAnimal study (in vivo)Efficacy outcome
In db/db mice, Kisspeptin‑54 treatment reduced albuminuria.
In plain wordsIn diabetic mice, Kisspeptin‑54 lowered the amount of albumin lost in urine.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseAlbuminuria
Study
mousen: not reported in source
db/db mice (type 2 diabetic nephropathy model)
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Kisspeptin-54 treatment in mice restored the junction protein ZO-1, reduced albuminuria and serum creatinine.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
Report a problemFND-4195074303
03AnimalAnimal study (in vivo)Efficacy outcome
In db/db mice, Kisspeptin‑54 treatment reduced serum creatinine.
In plain wordsIn diabetic mice, Kisspeptin‑54 lowered serum creatinine, a kidney marker.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseSerum creatinine
Study
mousen: not reported in source
db/db mice (type 2 diabetic nephropathy model)
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Kisspeptin-54 treatment in mice restored the junction protein ZO-1, reduced albuminuria and serum creatinine.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
Report a problemFND-4195074304
04LabIn vitro (cells)Efficacy outcome
In high-glucose-exposed human renal glomerular endothelial cells, Kisspeptin‑54 improved barrier integrity in a concentration-dependent way.
In plain wordsIn cells, Kisspeptin‑54 improved the strength of a kidney cell barrier, and more peptide gave more effect.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseEndothelial barrier integrity
Study
humann: not reported in source
human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
In HG-exposed cells, it concentration-dependently improved barrier integrity.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
Report a problemFND-4195074305
05LabIn vitro (cells)Mechanism
In high-glucose-exposed renal endothelial cells, Kisspeptin‑54 suppressed the upregulation of the transcriptional repressor ZEB1.
In plain wordsIn cells, Kisspeptin‑54 reduced the rise of ZEB1, a protein that represses barrier genes.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseZEB1 upregulation
Study
humann: not reported in source
human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, Kisspeptin-54 suppressed the upregulation of the transcriptional repressor ZEB1.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
Report a problemFND-4195074306

Natural levels measured1

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.

06AnimalEndogenous levelAnimal study (in vivo)Mechanism
In db/db mice and high-glucose-exposed renal endothelial cells, the natural Kisspeptin‑54/GPR54 pathway was impaired.
In plain wordsIn diabetic kidney disease models, the body's own Kisspeptin‑54 pathway was impaired.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseKisspeptin-54/GPR54 pathway in diabetic nephropathy models
Study
mouse and human cellsn: not reported in source
db/db mice and human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
The Kisspeptin-54/GPR54 pathway was impaired in DN models.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
This result measures the body's own Kisspeptin-54 (metastin). Nobody was given the peptide. It is not evidence about taking it.
Report a problemFND-4195074301

Studies that did not test the peptide alone3

In this study, Kisspeptin-54 (metastin) 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-54 (metastin).

07LabNot a test of Kisspeptin-54 (metastin) aloneIn vitro (cells)Mechanism
In renal endothelial cells, an ERK inhibitor blocked the suppression of ZEB1 by Kisspeptin‑54.
In plain wordsIn cells, blocking ERK stopped Kisspeptin‑54 from lowering ZEB1.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseKisspeptin-54 suppression of ZEB1 with ERK inhibitor
Study
humann: not reported in source
human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
This effect was blocked by ERK inhibition
2 context sentences(design, population, supporting numbers)
Summary · context
Mechanistically, Kisspeptin-54 suppressed the upregulation of the transcriptional repressor ZEB1.
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
In this study, Kisspeptin-54 (metastin) 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-54 (metastin).
Report a problemFND-4195074307
08LabNot a test of Kisspeptin-54 (metastin) aloneIn vitro (cells)Mechanism
In renal endothelial cells, siRNA knockdown of GPR54 abolished the benefits of Kisspeptin‑54.
In plain wordsIn cells, removing the GPR54 receptor stopped the benefits of Kisspeptin‑54.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseKisspeptin-54 benefits after GPR54 knockdown
Study
humann: not reported in source
human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
required GPR54, as siRNA knockdown abolished the benefits.
2 context sentences(design, population, supporting numbers)
Summary · context
Mechanistically, Kisspeptin-54 suppressed the upregulation of the transcriptional repressor ZEB1.
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
In this study, Kisspeptin-54 (metastin) 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-54 (metastin).
Report a problemFND-4195074308
09LabNot a test of Kisspeptin-54 (metastin) aloneIn vitro (cells)Mechanism
In renal endothelial cells, overexpression of ZEB1 reversed the protection provided by Kisspeptin‑54.
In plain wordsIn cells, raising ZEB1 levels reversed the protection that Kisspeptin‑54 gave.
Peptide
Kisspeptin-54 (metastin)
Outcome
DecreaseKisspeptin-54 protection after ZEB1 overexpression
Study
humann: not reported in source
human renal glomerular endothelial cells (HrGECs) exposed to high glucose
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
Overexpression of ZEB1 reversed the protection provided by Kisspeptin-54.
1 context sentence(design, population, supporting numbers)
Summary · context
This study used db/db mice (type 2 DN model) and human renal glomerular endothelial cells (HrGECs) exposed to high glucose (HG).
In this study, Kisspeptin-54 (metastin) 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-54 (metastin).
Report a problemFND-4195074309

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
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Journal Article

MeSH terms

Keywords

PepBank is a research reference. Talk to a doctor before you use any peptide.