Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy.

Liu J, Zhang M, Ge Y, Gunning W, Dworkin LD, Gong R

Molecular therapy : the journal of the American Society of Gene Therapy29 Jul 2025Cited by 9 (Europe PMC)

PMID40739753PMCIDPMC12636283DOI10.1016/j.ymthe.2025.07.046PepBankPUB-40739753

Read at source 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: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study8

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

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with THSD7A-associated membranous nephropathy, repository corticotropin injection attenuated proteinuria.
In plain wordsIn mice with membranous nephropathy, repository corticotropin injection reduced protein loss in urine.
Peptide
ACTH (corticotropin)
Outcome
DecreaseProteinuria
Study
mousen: not reported in source
Heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
Report a problemFND-4073975307
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with THSD7A-associated membranous nephropathy, repository corticotropin injection ameliorated glomerulopathy.
In plain wordsIn mice with membranous nephropathy, repository corticotropin injection improved disease of the kidney filters.
Peptide
ACTH (corticotropin)
Outcome
DecreaseGlomerulopathy
Study
mousen: not reported in source
Heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
Report a problemFND-4073975308

Studies that did not test the peptide alone6

In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).

03AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Efficacy outcome
In a mouse model of THSD7A-associated membranous nephropathy, pooled melanocortin agents (repository corticotropin injection, NDP-MSH and PG-901) attenuated proteinuria.
In plain wordsIn mice with membranous nephropathy, several melanocortin drugs together reduced protein loss in urine.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseProteinuria with pooled melanocortin agents
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975301
04AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Efficacy outcome
In a mouse model of THSD7A-associated membranous nephropathy, pooled melanocortin agents (repository corticotropin injection, NDP-MSH and PG-901) ameliorated glomerulopathy.
In plain wordsIn mice with membranous nephropathy, several melanocortin drugs together improved kidney filter damage.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseGlomerulopathy with pooled melanocortin agents
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975302
05AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In mice, knockout of the melanocortin 5 receptor gene exacerbated membranous nephropathy.
In plain wordsIn mice, removing the MC5R gene made membranous nephropathy worse.
Peptide
Melanotan I (afamelanotide)
Outcome
IncreaseMembranous nephropathy severity after MC5R knockout
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
In contrast, MC5R knockout exacerbated membranous nephropathy, while abolishing the beneficial effects of melanocortins.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975303
06AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In mice, MC5R knockout abolished the beneficial effects of melanocortins in membranous nephropathy.
In plain wordsIn mice, without the MC5R gene the melanocortin drugs no longer helped membranous nephropathy.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseMelanocortin benefit after MC5R knockout
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
In contrast, MC5R knockout exacerbated membranous nephropathy, while abolishing the beneficial effects of melanocortins.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975304
07AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In mice with membranous nephropathy, MC5R agonism diminished glomerular fixation of C5b-9 and C3, and MC5R knockout enhanced it.
In plain wordsIn mice, drugs that activate MC5R reduced complement build-up in the kidney filter, and losing MC5R increased it.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseGlomerular C5b-9 and C3 fixation with MC5R agonism
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Furthermore, glomerular fixation of C5b-9 and C3 was diminished by MC5R agonism but enhanced by MC5R knockout, despite comparable glomerular deposition of the heterologous nephritogenic antibody and activation of C4.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975305
08AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In mice, MC5R signaling inhibited podocyte expression of complement factors B and D through a PPARγ-dependent mechanism.
In plain wordsIn mice, MC5R signaling lowered kidney cell production of two complement proteins.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreasePodocyte expression of complement factors B and D
Study
mousen: not reported in source
heterologous mouse model of THSD7A-associated membranous nephropathy
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Comprehensive complement cascade analysis revealed that this anti-complement effect of MC5R signaling stems from an inhibition of podocyte expression of complement factors B and D, critical regulators of the complement amplification loop, involving a peroxisome proliferator-activated receptor gamma…
1 context sentence(design, population, supporting numbers)
Summary · context
Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated prot…
In this study, Melanotan I (afamelanotide) 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 Melanotan I (afamelanotide).
Report a problemFND-4073975306

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 3Current
27 Oct 2026, 16:35 UTC
Study data updated · source update from Europe PMC
Version 2
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.

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