High glucose promotes macrophage switching to the M1 phenotype via the downregulation of STAT-3 mediated autophagy.

Zhao Y, Jiang Y, Wang F, Sun L, Ding M, Zhang L, Wu B, Zhang X

PloS one31 Dec 2024Cited by 3 (Europe PMC)

PMID39739966PMCIDPMC11687880DOI10.1371/journal.pone.0314974PepBankPUB-39739966

Summary

AimImbalanced M1/M2 macrophage phenotype activation is a key point in diabetic kidney disease (DKD). Macrophages mainly exhibit the M1 phenotype, which contributes to inflammation and fibrosis in DKD. Studies have indicated that autophagy plays an important role in M1/M2 activation. However, the mechanism by which autophagy regulates the macrophage M1/M2 phenotype in DKD is unknown. Thus, the aim of the present study was to explore whether high glucose-induced macrophages switch to the M1 phenotype via the downregulation of STAT-3-mediated autophagy.MethodsDKD model rats were established in vivo via the intraperitoneal injection of streptozocin (STZ). The rats were sacrificed at 18 weeks for histological and molecular analysis. RAW264.7 cells were cultured in vitro with 30 mM glucose in the presence or absence of a STAT-3 activator (colivelin) and an autophagy activator (rapamycin). Moreover, M1 and M2 macrophage activation models were established as a control group. Immunofluorescence and Western blot analyses were used to detect the expression of autophagy-related proteins (LC3 and Beclin-1), M1 markers (iNOS and CD11c) and M2 markers (MR and CD206).ResultsIn DKD, macrophages exhibit an M1 phenotype. Under high-glucose conditions, RAW264.7 macrophages switched to the M1 phenotype. Autophagy was downregulated in high glucose-induced M1 macrophages. Both the STAT-3 activator and the autophagy activator promoted the transition of glucose-induced M1 macrophages to M2 macrophages. Moreover, STAT-3 activation increased the expression of autophagy markers (LC3 and Beclin-1). However, the autophagy activator had no effect on STAT-3 phosphorylation.ConclusionHigh glucose promotes macrophage switching to the M1 phenotype via the downregulation of STAT-3-mediated autophagy.

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

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Colivelin 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 Colivelin.

01LabNot a test of Colivelin aloneIn vitro (cells)Mechanism
In high-glucose RAW264.7 macrophages, the STAT-3 activator colivelin promoted transition from the M1 to M2 phenotype.
In plain wordsIn cells exposed to high glucose, colivelin promoted a change from M1 to M2 macrophages.
Peptide
Colivelin
Outcome
IncreaseM1 to M2 macrophage transition
Study
n: not reported in source
high-glucose RAW264.7 macrophages
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Both the STAT-3 activator and the autophagy activator promoted the transition of glucose-induced M1 macrophages to M2 macrophages.
1 context sentence(design, population, supporting numbers)
Summary · context
RAW264.7 cells were cultured in vitro with 30 mM glucose in the presence or absence of a STAT-3 activator (colivelin) and an autophagy activator (rapamycin).
In this study, Colivelin 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 Colivelin.
Show in the study text Report a problemFND-3973996601
02LabNot a test of Colivelin aloneIn vitro (cells)Mechanism
In high-glucose RAW264.7 macrophages, STAT-3 activation with colivelin increased LC3 expression.
In plain wordsIn cells exposed to high glucose, STAT-3 activation with colivelin increased LC3 expression.
Peptide
Colivelin
Outcome
IncreaseLC3 expression
Study
n: not reported in source
high-glucose RAW264.7 macrophages
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
Moreover, STAT-3 activation increased the expression of autophagy markers (LC3 and Beclin-1).
1 context sentence(design, population, supporting numbers)
Summary · context
RAW264.7 cells were cultured in vitro with 30 mM glucose in the presence or absence of a STAT-3 activator (colivelin) and an autophagy activator (rapamycin).
In this study, Colivelin 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 Colivelin.
Show in the study text Report a problemFND-3973996602
03LabNot a test of Colivelin aloneIn vitro (cells)Mechanism
In high-glucose RAW264.7 macrophages, STAT-3 activation with colivelin increased Beclin-1 expression.
In plain wordsIn cells exposed to high glucose, STAT-3 activation with colivelin increased Beclin-1 expression.
Peptide
Colivelin
Outcome
IncreaseBeclin-1 expression
Study
n: not reported in source
high-glucose RAW264.7 macrophages
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
Moreover, STAT-3 activation increased the expression of autophagy markers (LC3 and Beclin-1).
1 context sentence(design, population, supporting numbers)
Summary · context
RAW264.7 cells were cultured in vitro with 30 mM glucose in the presence or absence of a STAT-3 activator (colivelin) and an autophagy activator (rapamycin).
In this study, Colivelin 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 Colivelin.
Show in the study text Report a problemFND-3973996603

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
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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