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.
■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。