College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Int J Biol Sci. 2021 Oct 17;17(15):4271-4284. doi: 10.7150/ijbs.62380. eCollection 2021.
Mastitis causes great psychological and physical pain among women. Our previous studies found that niacin has anti-inflammatory effect, and the realization of this function depends on GPR109A. However, there are no previous reports about the anti-inflammatory function of GPR109A in mastitis. In our study, we observed the effect of niacin on the WT and GPR109A mice mastitis model. The results showed that administration of niacin to WT mice reduced the damage, proinflammatory mediators and protected the integrity of the blood milk barrier in mammary gland. While in GPR109A mice, there was no effect on the above indexes. In mammary epithelial cells, GPR109A was able to promote autophagy and Nrf2 nuclear import through AMPK. In LPS-induced mammary epithelial cells, niacin inhibited the LPS-induced inflammatory response and downregulation of tight junction proteins, and these effects were eliminated by knocking down GPR109A, blocking autophagy or inhibiting Nrf2 nuclear import. These results indicate that in mastitis, GPR109A promotes autophagy and Nrf2 nuclear import through AMPK, thereby inhibiting inflammatory damage to the mammary gland and repairing the blood milk barrier. Our results suggested that GPR109A may be a potential target for the treatment of mastitis.
乳腺炎会给女性带来巨大的心理和生理痛苦。我们之前的研究发现，烟酸具有抗炎作用，而这一功能的实现依赖于 GPR109A。然而，目前尚无关于 GPR109A 在乳腺炎中抗炎功能的报道。在本研究中，我们观察了烟酸对 WT 和 GPR109A 小鼠乳腺炎模型的作用。结果表明，给予 WT 小鼠烟酸可减轻损伤、促炎介质并保护乳腺中血乳屏障的完整性。而在 GPR109A 小鼠中，上述指标均无变化。在乳腺上皮细胞中，GPR109A 能够通过 AMPK 促进自噬和 Nrf2 核转位。在 LPS 诱导的乳腺上皮细胞中，烟酸抑制 LPS 诱导的炎症反应和紧密连接蛋白的下调，而这些作用被敲低 GPR109A、阻断自噬或抑制 Nrf2 核转位所消除。这些结果表明，在乳腺炎中，GPR109A 通过 AMPK 促进自噬和 Nrf2 核转位，从而抑制乳腺的炎症损伤并修复血乳屏障。我们的研究结果表明，GPR109A 可能是治疗乳腺炎的潜在靶点。
