Fukuoka Cíntia Yuki, Simões Alyne, Uchiyama Toshikazu, Arana-Chavez Victor Elias, Abiko Yoshimitsu, Kuboyama Noboru, Bhawal Ujjal K
Department of Biomaterials and Oral Biology, São Paulo University, School of Dentistry, São Paulo, Brazil.
Department of Social Dentistry (Medical Informatics), Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
PLoS One. 2017 Jan 18;12(1):e0169443. doi: 10.1371/journal.pone.0169443. eCollection 2017.
Diabetes can lead to dysfunction of the secretory capacity in salivary glands. Activation of the receptor for advanced glycation end products (RAGE) and its ligands has been suggested to participate in chronic disorders such as diabetes and its complications. In this study, the expression of RAGE, high mobility group box 1 (HMGB1) and advanced glycation end products (AGE), as well as the effects of low-power laser irradiation (LPLI) in salivary glands of diabetic rats were evaluated, and the mechanisms involved were characterized. The expression of RAGE and HMGB1 at the protein and mRNA levels was observed in submandibular glands (SMGs) of streptozotocin-induced diabetic rats. A diode laser was applied at 660 nm, 70 mW, 20 J/cm2, 0.56 J/point, with a spot area of 0.028 cm2 and its in vivo effects and the pathways involved were evaluated. Immunohistochemistry and western blotting analysis were performed for inflammatory and apoptosis markers. Diabetes up-regulates HMGB1/AGE/RAGE axis gene expression in SMGs that is associated with activation of the nuclear factor kappa B (NF-κB) pathway. Interestingly, LPLI suppresses NF-κB activation induced by inflammation. LPLI also reduces diabetes-induced apoptosis. That effect was accompanied by decreased levels of Bax, and cleaved caspase 3, which were up-regulated in diabetes. Taken together, our data suggest that LPLI reduces diabetes-induced inflammation by reducing the induction of HMGB1, ultimately leading to inhibition of apoptosis in submandibular glands of diabetic rats.
糖尿病可导致唾液腺分泌功能障碍。晚期糖基化终末产物受体（RAGE）及其配体的激活被认为参与了糖尿病及其并发症等慢性疾病。在本研究中，评估了糖尿病大鼠唾液腺中RAGE、高迁移率族蛋白B1（HMGB1）和晚期糖基化终末产物（AGE）的表达，以及低功率激光照射（LPLI）的作用，并对其相关机制进行了表征。观察了链脲佐菌素诱导的糖尿病大鼠下颌下腺（SMG）中RAGE和HMGB1在蛋白质和mRNA水平的表达。应用波长为660 nm、功率为70 mW、能量密度为20 J/cm²、每点能量为0.56 J、光斑面积为0.028 cm²的二极管激光，并评估其体内效应及相关途径。对炎症和凋亡标志物进行了免疫组织化学和蛋白质印迹分析。糖尿病上调了SMG中HMGB1/AGE/RAGE轴基因的表达，这与核因子κB（NF-κB）途径的激活有关。有趣的是，LPLI抑制了炎症诱导的NF-κB激活。LPLI还减少了糖尿病诱导的细胞凋亡。这种作用伴随着Bax和裂解的半胱天冬酶3水平的降低，而这两种蛋白在糖尿病中表达上调。综上所述，我们的数据表明，LPLI通过减少HMGB1的诱导来减轻糖尿病诱导的炎症，最终导致糖尿病大鼠下颌下腺细胞凋亡的抑制。
