Diabetes-related intestinal region-specific thickening of ganglionic basement membrane and regionally decreased matrix metalloproteinase 9 expression in myenteric ganglia

作     者：Nikolett Bódi Diána Mezei Payal Chakraborty Zita Szalai Bence Pál Barta János Balázs Zsolt Rázga Edit Hermesz Mária Bagyánszki 

作者机构：Department of PhysiologyAnatomy and NeuroscienceFaculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of Biochemistry and Molecular BiologyFaculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of PathologyFaculty of MedicineUniversity of SzegedSzeged 6720Hungary 

出 版 物：《World Journal of Diabetes》 (世界糖尿病杂志（英文版）（电子版）)

年 卷 期：2021年第12卷第5期

页      面：658-672页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：European Union and the Hungarian Government in the framework,No.EFOP-3.6.1-16-2016-00008 Hungarian NKFIH fund project,No.FK131789(to Bódi N) János Bolyai Research Scholarship of the Hungarian Academy of Sciences(to Bódi N) and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research,Development and Innovation Fund,No.ÚNKP-20-5(to Bódi N) 

主　　题：Type 1 diabetes Diabetic enteric neuropathy Neuronal microenvironment Basement membrane Matrix metalloproteinase 9 Tissue inhibitor of metalloproteinase 1 

摘      要：BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9(MMP9) and its tissue inhibitor(TIMP1) are essential in regulating extracellular matrix *** To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 *** Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex-and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Wholemount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid(m RNA) level was measured by quantitative polymerase chain *** Ten weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tenden