PMID- 37401390
OWN - NLM
STAT- MEDLINE
DCOM- 20230809
LR  - 20230816
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 325
IP  - 2
DP  - 2023 Aug 1
TI  - Gremlin 1 is required for macrophage M2 polarization.
PG  - L270-L276
LID - 10.1152/ajplung.00163.2023 [doi]
AB  - Pro-proliferative, M2-like polarization of macrophages is a critical step in the 
      development of fibrosis and remodeling in chronic lung diseases such as pulmonary 
      fibrosis and pulmonary hypertension. Macrophages in healthy and diseased lungs 
      express gremlin 1 (Grem1), a secreted glycoprotein that acts in both paracrine 
      and autocrine manners to modulate cellular function. Increased Grem1 expression 
      plays a central role in pulmonary fibrosis and remodeling, however, the role of 
      Grem1 in M2-like polarization of macrophages has not previously been explored. 
      The results reported here show that recombinant Grem1 potentiated M2-like 
      polarization of mouse macrophages and bone marrow-derived macrophages (BMDMs) in 
      response to the Th2 cytokines IL4 and IL13. Genetic depletion of Grem1 in BMDMs 
      inhibited M2 polarization while exogenous gremlin 1 could partially rescue this 
      effect. Taken together, these findings reveal that gremlin 1 is required for 
      M2-like polarization of macrophages.NEW & NOTEWORTHY We show here that gremlin 1 
      potentiated M2 polarization of mouse bone marrow-derived macrophages (BMDMs) in 
      response to the Th2 cytokines IL4 and IL13. Genetic depletion of Grem1 in BMDMs 
      inhibited M2 polarization while exogenous gremlin 1 partially rescued this 
      effect. Taken together, these findings reveal a previously unknown requirement 
      for gremlin 1 in M2 polarization of macrophages and suggest a novel cellular 
      mechanism promoting fibrosis and remodeling in lung diseases.
FAU - Mthunzi, Liberty
AU  - Mthunzi L
AUID- ORCID: 0000-0002-4636-4884
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
FAU - Rowan, Simon C
AU  - Rowan SC
AUID- ORCID: 0000-0002-4103-4421
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
FAU - Kostyunina, Daria S
AU  - Kostyunina DS
AUID- ORCID: 0000-0003-0842-2526
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
FAU - Baugh, John A
AU  - Baugh JA
AUID- ORCID: 0000-0002-5357-5575
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
FAU - Knaus, Ulla G
AU  - Knaus UG
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
FAU - McLoughlin, Paul
AU  - McLoughlin P
AUID- ORCID: 0000-0001-6200-016X
AD  - School of Medicine, Health Sciences Centre, University College Dublin, Dublin, 
      Ireland.
LA  - eng
SI  - figshare/10.6084/m9.figshare.23678034
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230704
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Interleukin-13)
RN  - 0 (Cytokines)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Pulmonary Fibrosis/genetics/metabolism
MH  - Interleukin-4/genetics/pharmacology/metabolism
MH  - Interleukin-13/metabolism
MH  - Macrophages/metabolism
MH  - Cytokines/metabolism
MH  - Fibrosis
OTO - NOTNLM
OT  - M2 polarization
OT  - fibrosis
OT  - gremlin 1
OT  - macrophage
OT  - remodeling
EDAT- 2023/07/04 06:42
MHDA- 2023/08/09 06:43
CRDT- 2023/07/04 04:03
PHST- 2023/08/09 06:43 [medline]
PHST- 2023/07/04 06:42 [pubmed]
PHST- 2023/07/04 04:03 [entrez]
AID - 10.1152/ajplung.00163.2023 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2023 Aug 1;325(2):L270-L276. doi: 
      10.1152/ajplung.00163.2023. Epub 2023 Jul 4.