TY - JOUR
T1 - Macrophage motility in wound healing is regulated by hif‐1α via s1p signaling
AU - Hutami, Islamy Rahma
AU - Izawa, Takashi
AU - Khurel‐ochir, Tsendsuren
AU - Sakamaki, Takuma
AU - Iwasa, Akihiko
AU - Tanaka, Eiji
N1 - Funding Information:
Funding: This work was supported in part by JSPS KAKENHI grants from the Japan Society for the Promotion of Science (No. 18H03011 to T.I.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/2
Y1 - 2021/8/2
N2 - Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subse-quently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)‐1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF‐1α regulates sphingosine 1‐phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF‐ 1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF‐ 1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of mon-ocytes/macrophages in response to circulating HIF‐1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing.
AB - Accumulating evidence indicates that the molecular pathways mediating wound healing induce cell migration and localization of cytokines to sites of injury. Macrophages are immune cells that sense and actively respond to disturbances in tissue homeostasis by initiating, and subse-quently resolving, inflammation. Hypoxic conditions generated at a wound site also strongly recruit macrophages and affect their function. Hypoxia inducible factor (HIF)‐1α is a transcription factor that contributes to both glycolysis and the induction of inflammatory genes, while also being critical for macrophage activation. For the latter, HIF‐1α regulates sphingosine 1‐phosphate (S1P) to affect the migration, activation, differentiation, and polarization of macrophages. Recently, S1P and HIF‐ 1α have received much attention, and various studies have been performed to investigate their roles in initiating and resolving inflammation via macrophages. It is hypothesized that the HIF‐ 1α/S1P/S1P receptor axis is an important determinant of macrophage function under inflammatory conditions and during disease pathogenesis. Therefore, in this review, biological regulation of mon-ocytes/macrophages in response to circulating HIF‐1α is summarized, including signaling by S1P/S1P receptors, which have essential roles in wound healing.
KW - HIF1
KW - M1/M2 macrophage
KW - S1P
KW - Wound healing
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U2 - 10.3390/ijms22168992
DO - 10.3390/ijms22168992
M3 - Article
C2 - 34445695
AN - SCOPUS:85113222197
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 16
M1 - 8992
ER -