Abstract：
UNASSIGNED: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment.
UNASSIGNED: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.
UNASSIGNED: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results.
UNASSIGNED: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.
UNASSIGNED: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.
UNASSIGNED: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results.
UNASSIGNED: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.
摘要：
■Gremlin1是一种多功能蛋白，其表达被证明参与一系列生理和病理过程。已经建立了Gremlin1与筋膜牙周炎（AP）之间的关联。M1极化巨噬细胞是加重根尖牙周炎性反应进展的关键免疫细胞,但Gremlin1在根尖周病变巨噬细胞激活过程中的功能仍不清楚。本研究试图探讨Gremlin1对根尖周炎微环境中巨噬细胞极化的调节作用。
■临床标本用于通过免疫组织化学（IHC）染色确定Gremlin1在根尖周组织中的表达。然后，建立大鼠根尖周炎性疾病模型,和腺病毒相关病毒(AAV)用于阻断Gremlin1表达。携带sh-Gremlin1颗粒的慢病毒用于转染THP-1诱导的M1亚型巨噬细胞。为了评估相关分子的表达，Western-blot,进行免疫荧光染色。
■Gremlin1在通过IHC染色鉴定的AP受试者的根尖周组织中显著上调，与M1巨噬细胞相关基因水平呈正相关。在根尖周病变中抑制Gremlin1的大鼠AP模型显示出巨噬细胞的有限浸润和M1巨噬细胞相关基因在根尖周病变中的表达降低。此外，Gremlin1阻断显著降低了Notch1/Hes1信号通路的激活水平。体外实验证实了上述结果。
■放在一起，目前的研究表明，根尖周病变中的Gremlin1抑制抑制了M1巨噬细胞通过Notch1/Hes1轴的极化。此外，Gremlin1可能是治疗AP的潜在候选者。
■临床标本用于通过免疫组织化学（IHC）染色确定Gremlin1在根尖周组织中的表达。然后，建立大鼠根尖周炎性疾病模型,和腺病毒相关病毒(AAV)用于阻断Gremlin1表达。携带sh-Gremlin1颗粒的慢病毒用于转染THP-1诱导的M1亚型巨噬细胞。为了评估相关分子的表达，Western-blot,进行免疫荧光染色。
■Gremlin1在通过IHC染色鉴定的AP受试者的根尖周组织中显著上调，与M1巨噬细胞相关基因水平呈正相关。在根尖周病变中抑制Gremlin1的大鼠AP模型显示出巨噬细胞的有限浸润和M1巨噬细胞相关基因在根尖周病变中的表达降低。此外，Gremlin1阻断显著降低了Notch1/Hes1信号通路的激活水平。体外实验证实了上述结果。
■放在一起，目前的研究表明，根尖周病变中的Gremlin1抑制抑制了M1巨噬细胞通过Notch1/Hes1轴的极化。此外，Gremlin1可能是治疗AP的潜在候选者。
