Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P17931 (
galectin-3
)
2,860
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background We previously reported that osteopontin plays an essential role in accelerating both reparative fibrosis and clearance of dead cells (efferocytosis) during tissue repair after myocardial infarction (MI) and
galectin-3
hi
CD206
+
macrophages is the main source of osteopontin in post-MI heart. Interleukin-10- STAT3 (signal transducer and activator of transcription 3)-
galectin-3
axis is essential for
Spp1
(encoding osteopontin) transcriptional activation in cardiac macrophages after MI. Here, we investigated the more detailed mechanism responsible for functional maturation of osteopontin-producing macrophages. Methods and Results In post-MI hearts,
Spp1
transcriptional activation occurred almost exclusively in MerTK (Mer tyrosine kinase)
+
galectin-3
hi
macrophages. The induction of MerTK on
galectin-3
hi
macrophages is essential for their functional maturation including efferocytosis and
Spp1
transcriptional activity. MerTK
+
galectin-3
hi
macrophages showed a strong activation of both STAT3 and ERK (extracellular signal-regulated kinase). STAT3 inhibition suppressed the differentiation of osteopontin-producing MerTK
+
galectin-3
hi
macrophages, however, STAT3 activation was insufficient at inducing
Spp1
transcriptional activity. ERK inhibition suppressed
Spp1
transcriptional activation without affecting MerTK or
galectin-3
expression. Concomitant activation of ERK is required for transcriptional activation of
Spp1
. In
Il-10
knockout enhanced green fluorescent protein-
Spp1
knock-in mice subjected to MI, osteopontin-producing macrophages decreased but did not disappear entirely. Interleukin-10 and macrophage colony-stimulating factor synergistically activated STAT3 and ERK and promoted the differentiation of osteopontin-producing MerTK
+
galectin-3
hi
macrophages in bone marrow-derived macrophages. Coadministration of anti-interleukin-10 plus anti-macrophage colony-stimulating factor antibodies substantially reduced the number of osteopontin-producing macrophages by more than anti-interleukin-10 antibody alone in post-MI hearts. Conclusions Interleukin-10 and macrophage colony-stimulating factor act synergistically to activate STAT3 and ERK in cardiac macrophages, which in turn upregulate the expression of
galectin-3
and MerTK, leading to the functional maturation of osteopontin-producing macrophages.
...
PMID:MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction. 3286 99
