Department of Oral Growth & Development, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, 814-0193, Japan.
Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-0914, Japan.
BMC Nephrol. 2021 Jan 6;22(1):3. doi: 10.1186/s12882-020-02203-y.
The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in diabetic mouse kidneys with periodontal pathogen Pg-LPS-induced nephropathy.
We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (Pg-LPS) induce nephropathy in diabetic mice. It is thought that Pg-LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of Pg-LPS via TLR in the diabetic kidneys. There have been no reports of the effects of periodontopathic bacteria on the expression of leukocyte adhesion molecules and the accumulation of physiologically active substances in the kidney.
The immunohistochemical investigation was performed on diabetic mouse kidney with Pg-LPS-induced nephropathy with glomerulosclerosis in glomeruli.
There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), or in healthy ICR mice administered Pg-LPS (LPS-ICR). However, in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ) the expression of VCAM-1 and the accumulation of FGF23 were observed in renal tubules and glomeruli, and the expression of E-selectin was observed in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions of ICR, STZ-ICR, or LPS-ICR. In LPS-STZ ACE2 was detected both in renal tubules as well as in glomeruli. The Mac-1 and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was the distribution of a large number of Mac-1-positive cells in LPS-STZ.
The Pg-LPS may induce diabetic renal inflammation such as glomerulosclerosis and tubulitis with infiltration of Mac-1/podoplanin positive macrophages via glomerular overexpression of VCAM-1 and E-selectin, resulting in accumulation of both ACE2 and FGF23 which were unmetabolized with the inflammation-induced kidney damage under the diabetic condition. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.
本研究旨在探讨白细胞黏附分子和肾脏代谢因子在牙周致病菌 Pg-LPS 诱导的糖尿病小鼠肾脏病变中的表达。
我们最近报道称，在糖尿病环境中，肾小球内皮细胞表达 Toll 样受体（TLR）2 和 TLR4，TLR2/4 配体牙龈卟啉单胞菌脂多糖（Pg-LPS）可诱导糖尿病小鼠发生肾病。据认为，Pg-LPS 通过糖尿病肾脏中的 TLR 识别 Pg-LPS，促进白细胞黏附分子的过度表达和肾脏特异性代谢酶的慢性炎症，从而导致炎症反应。目前还没有关于牙周病细菌对白细胞黏附分子表达和肾脏中生理活性物质积累的影响的报道。
采用免疫组织化学方法检测肾小球硬化性 Pg-LPS 诱导的糖尿病小鼠肾脏中白细胞黏附分子和生理活性物质的表达。
在链脲佐菌素（STZ）诱导的糖尿病 ICR 小鼠（STZ-ICR）或给予 Pg-LPS 的健康 ICR 小鼠（LPS-ICR）中，均未观察到血管细胞黏附分子-1（VCAM-1）、E-选择素或成纤维细胞生长因子 23（FGF23）在血管中表达。然而，在 Pg-LPS 诱导的糖尿病 ICR 小鼠肾脏病变（LPS-STZ）中，VCAM-1 的表达和 FGF23 的积累在肾小管和肾小球中观察到，E-选择素在肾实质和肾小球中观察到。血管紧张素转换酶 2（ACE2）在近端小管中检测到，但在 ICR、STZ-ICR 或 LPS-ICR 的其他区域未检测到。在 LPS-STZ 中，ACE2 不仅在肾小管中，而且在肾小球中均有表达。在糖尿病状态下，Mac-1 和 podoplanin 阳性细胞在肾实质中增加，在 LPS-STZ 中有大量的 Mac-1 阳性细胞分布。
Pg-LPS 可能通过肾小球 VCAM-1 和 E-选择素的过度表达，诱导糖尿病肾脏炎症，如肾小球硬化和小管炎，并伴有 Mac-1/podoplanin 阳性巨噬细胞浸润，导致 ACE2 和 FGF23 的积累，在糖尿病状态下，这些物质未被代谢，导致炎症引起的肾脏损伤。牙周炎可能是糖尿病患者肾病进展的一个关键因素。
