PMID- 36177049
OWN - NLM
STAT- MEDLINE
DCOM- 20221003
LR  - 20221003
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Reprogramming alternative macrophage polarization by GATM-mediated endogenous 
      creatine synthesis: A potential target for HDM-induced asthma treatment.
PG  - 937331
LID - 10.3389/fimmu.2022.937331 [doi]
LID - 937331
AB  - Cellular energy metabolism plays a crucial role in the regulation of macrophage 
      polarization and in the execution of immune functions. A recent study showed that 
      Slc6a8-mediated creatine uptake from exogenous supplementation modulates 
      macrophage polarization, yet little is known about the role of the de novo 
      creatine de novobiosynthesis pathway in macrophage polarization. Here, we 
      observed that glycine amidinotransferase (GATM), the rate-limiting enzyme for 
      creatine synthesis, was upregulated in alternative (M2) polarized macrophages, 
      and was dependent on the transcriptional factor STAT6, whereas GATM expression 
      was suppressed in the classical polarized (M1) macrophage. Next, we revealed that 
      exogenous creatine supplementation enhanced IL-4-induced M2 polarization, 
      confirming recent work. Furthermore, we revealed that genetic ablation of GATM 
      did not affect expression of M1 marker genes (Nos2, IL1b, IL12b) or the 
      production of nitric oxide in both peritoneal macrophages (PMs) and bone 
      marrow-derived macrophages (BMDMs). By contrast, expression levels of M2 markers 
      (Arg1, Mrc1, Ccl17 and Retnla) were lower following GATM deletion. Moreover, we 
      found that deletion of GATM in resident alveolar macrophages (AMs) significantly 
      blocked M2 polarization but with no obvious effect on the number of cells in 
      knockout mice. Lastly, an upregulation of GATM was found in lung tissue and 
      bronchoalveolar lavage fluid macrophages from HDM-induced asthmatic mice. Our 
      study uncovers a previously uncharacterized role for the de novo creatine 
      biosynthesis enzyme GATM in M2 macrophage polarization, which may be involved in 
      the pathogenesis of related inflammatory diseases such as an T helper 2 
      (Th2)-associated allergic asthma.
CI  - Copyright (c) 2022 Yu, Wang, Hu, Ren, Qiu, Li, Zhou, Chen and Chen.
FAU - Yu, Li
AU  - Yu L
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Wang, Lingwei
AU  - Wang L
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Hu, Guang
AU  - Hu G
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Ren, Laibin
AU  - Ren L
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Qiu, Chen
AU  - Qiu C
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Li, Shun
AU  - Li S
AD  - Department of Animal Model, Shanghai Public Health Clinical Center, Fudan 
      University, Shanghai, China.
FAU - Zhou, Xiaohui
AU  - Zhou X
AD  - Department of Animal Model, Shanghai Public Health Clinical Center, Fudan 
      University, Shanghai, China.
FAU - Chen, Shanze
AU  - Chen S
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
FAU - Chen, Rongchang
AU  - Chen R
AD  - Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital 
      (Shenzhen People's Hospital) and School of Medicine, Southern University of 
      Science and Technology, Shenzhen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220913
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 207137-56-2 (Interleukin-4)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.1.4.- (Amidinotransferases)
RN  - EC 2.1.4.1 (glycine amidinotransferase)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Amidinotransferases
MH  - Animals
MH  - *Asthma
MH  - *Creatine/metabolism
MH  - Interleukin-4/metabolism
MH  - Macrophages
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/metabolism
PMC - PMC9513582
OTO - NOTNLM
OT  - asthma
OT  - creatine
OT  - glycine amidinotransferase (GATM)
OT  - macrophage
OT  - polarization
COIS- The reviewer ZJ declared a shared parent affiliation with the authors, WZ, SL, to 
      the handling editor at the time of the review. The remaining authors declare that 
      the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2022/10/01 06:00
MHDA- 2022/10/04 06:00
PMCR- 2022/01/01
CRDT- 2022/09/30 02:41
PHST- 2022/05/06 00:00 [received]
PHST- 2022/08/22 00:00 [accepted]
PHST- 2022/09/30 02:41 [entrez]
PHST- 2022/10/01 06:00 [pubmed]
PHST- 2022/10/04 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.937331 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 13;13:937331. doi: 10.3389/fimmu.2022.937331. eCollection 
      2022.