RT Journal Article
SR Electronic
T1 The Role of mPGES-1 in Promoting Granulation Tissue Angiogenesis Through Regulatory T-cell Accumulation
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 2061
OP 2073
DO 10.21873/invivo.12932
VO 36
IS 5
A1 TETSUYA HYODO
A1 YOSHIYA ITO
A1 KANAKO HOSONO
A1 SATOSHI UEMATSU
A1 SHIZUO AKIRA
A1 MASATAKA MAJIMA
A1 AKIRA TAKEDA
A1 HIDEKI AMANO
YR 2022
UL http://iv.iiarjournals.org/content/36/5/2061.abstract
AB Background/Aim: Microsomal prostaglandin E synthase-1 (mPGES-1) is an enzyme, which catalyzes the final step of prostaglandin E2 (PGE2) synthesis. PGE2 in involved in wound-induced angiogenesis. Regulatory T cells (Tregs) regulate not only immune tolerance but also tissue repair and angiogenesis. We examined whether the mPGES-1/PGE2 axis contributes to wound-induced angiogenesis and granulation tissue formation through Treg accumulation. Materials and Methods: The dorsal subcutaneous tissues of male mPGES-1-deficient (mPGES-1−/−) and C57BL/6 wild-type (WT) mice were implanted with polyurethane sponge disks. Angiogenesis was estimated by determining the wet weight of sponge tissues and the expression of proangiogenic factors including CD31, vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β) in granulation tissues. Results: Angiogenesis was suppressed in mPGES-1−/− mice compared with WT mice, which was associated with attenuated forkhead box P3 (Foxp3) expression and Foxp3+ Treg accumulation. The number of cells double-positive for Foxp3/TGFβ and Foxp3/VEGF were lower in mPGES-1−/− mice than in WT mice. Neutralizing Tregs with antibodies (Abs) against CD25 or folate receptor 4 (FR4) inhibited the Foxp3+ Treg angiogenesis and accumulation in WT mice, but not in mPGES-1−/− mice. The topical application of PGE2 into the implanted sponge enhanced angiogenesis and accumulation of Tregs expressing TGFβ and VEGF in WT and mPGES-1−/− mice. Conclusion: Tregs producing TGFβ and VEGF accumulate in wounds and contribute to angiogenesis through mPGES-1-derived PGE2. mPGES-1 induction may control angiogenesis in skin wounds by recruiting Tregs.