Polarized macrophages promote gestational beta cell growth through extracellular signal-regulated kinase 5 signalling.
Diabetes Obes Metab
; 24(9): 1721-1733, 2022 09.
Article
in En
| MEDLINE
| ID: mdl-35546452
ABSTRACT
AIM:
To show that depletion of pancreatic macrophages impairs gestational beta cell proliferation and leads to glucose intolerance. MATERIALS ANDMETHODS:
Genetic animal models were applied to study the effects of depletion of pancreatic macrophges on gestational beta-cell proliferaiton and glucose response. The crosstalk between macrophages and beta-cells was studied in vivo using beta-cell-specific extracellular-signal-regulated kinase 5 (ERK5) knockout and epidermal growth receptor (EGFR) knockout mice, and in vitro using a co-culture system.RESULTS:
Beta cell-derived placental growth factor (PlGF) recruited naïve macrophages and polarized them towards an M2-like phenotype. These macrophages then secreted epidermal growth factor (EGF), which activated extracellular signal-regulated kinase 5 (ERK5) signalling in beta cells to promote gestational beta cell proliferation. On the other hand, activation of ERK5 signalling in beta cells likely, in turn, enhanced the production and secretion of PlGF by beta cells.CONCLUSIONS:
Our study shows a regulatory loop between macrophages and beta cells through PlGF/EGF/ERK5 signalling cascades to regulate gestational beta cell growth.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitogen-Activated Protein Kinase 7
/
Epidermal Growth Factor
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Diabetes Obes Metab
Journal subject:
ENDOCRINOLOGIA
/
METABOLISMO
Year:
2022
Document type:
Article