PMID- 30070144
OWN - NLM
STAT- MEDLINE
DCOM- 20200818
LR  - 20200818
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Linking)
VI  - 30
IP  - 12
DP  - 2019 Apr 20
TI  - The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on 
      Skeletal Muscle Regeneration.
PG  - 1553-1598
LID - 10.1089/ars.2017.7420 [doi]
AB  - Significance: Macrophages are crucial for tissue homeostasis. Based on their 
      activation, they might display classical/M1 or alternative/M2 phenotypes. M1 
      macrophages produce pro-inflammatory cytokines, reactive oxygen species (ROS), 
      and nitric oxide (NO). M2 macrophages upregulate arginase-1 and reduce NO and ROS 
      levels; they also release anti-inflammatory cytokines, growth factors, and 
      polyamines, thus promoting angiogenesis and tissue healing. Moreover, M1 and M2 
      display key metabolic differences; M1 polarization is characterized by an 
      enhancement in glycolysis and in the pentose phosphate pathway (PPP) along with a 
      decreased oxidative phosphorylation (OxPhos), whereas M2 are characterized by an 
      efficient OxPhos and reduced PPP. Recent Advances: The glutamine-related 
      metabolism has been discovered as crucial for M2 polarization. Vice versa, flux 
      discontinuities in the Krebs cycle are considered additional M1 features; they 
      lead to increased levels of immunoresponsive gene 1 and itaconic acid, to 
      isocitrate dehydrogenase 1-downregulation and to succinate, citrate, and 
      isocitrate over-expression. Critical Issues: A macrophage classification problem, 
      particularly in vivo, originating from a gap in the knowledge of the several 
      intermediate polarization statuses between the M1 and M2 extremes, characterizes 
      this field. Moreover, the detailed features of metabolic reprogramming crucial 
      for macrophage polarization are largely unknown; in particular, the role of 
      beta-oxidation is highly controversial. Future Directions: Manipulating the 
      metabolism to redirect macrophage polarization might be useful in various 
      pathologies, including an efficient skeletal muscle regeneration. Unraveling the 
      complexity pertaining to metabolic signatures that are specific for the different 
      macrophage subsets is crucial for identifying new compounds that are able to 
      trigger macrophage polarization and that might be used for therapeutical 
      purposes.
FAU - De Santa, Francesca
AU  - De Santa F
AD  - Institute of Cell Biology and Neurobiology (IBCN), National Research Council 
      (CNR), Rome, Italy.
FAU - Vitiello, Laura
AU  - Vitiello L
AD  - Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, 
      IRCCS San Raffaele Pisana, Rome, Italy.
FAU - Torcinaro, Alessio
AU  - Torcinaro A
AD  - Institute of Cell Biology and Neurobiology (IBCN), National Research Council 
      (CNR), Rome, Italy.
AD  - Department of Biology and Biotechnology "Charles Darwin," Sapienza University, 
      Rome, Italy.
FAU - Ferraro, Elisabetta
AU  - Ferraro E
AD  - Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, 
      IRCCS San Raffaele Pisana, Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20181009
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
SB  - IM
MH  - Animals
MH  - Cell Polarity
MH  - Humans
MH  - Macrophages/*physiology
MH  - Mitochondria/metabolism
MH  - Muscle, Skeletal/cytology/*physiology
MH  - Phenotype
MH  - *Regeneration
OTO - NOTNLM
OT  - cross-talk muscle-macrophages
OT  - macrophage polarization
OT  - metabolic reprogramming
OT  - mitochondria
OT  - rehabilitation
OT  - skeletal muscle regeneration
EDAT- 2018/08/03 06:00
MHDA- 2020/08/19 06:00
CRDT- 2018/08/03 06:00
PHST- 2018/08/03 06:00 [pubmed]
PHST- 2020/08/19 06:00 [medline]
PHST- 2018/08/03 06:00 [entrez]
AID - 10.1089/ars.2017.7420 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2019 Apr 20;30(12):1553-1598. doi: 10.1089/ars.2017.7420. 
      Epub 2018 Oct 9.