Gut region-specific TNFR expression:TNFR2 is more affected than TNFR1 in duodenal myenteric ganglia of diabetic rats  

作　　者：Bence Pál Barta Benita Onhausz Afnan AL Doghmi Zita Szalai János Balázs Mária Bagyánszki Nikolett Bódi 

机构地区：[1]Department of Physiology,Anatomy and Neuroscience,University of Szeged,Szeged 6726,Hungary

出　　处：《World Journal of Diabetes》2023年第1期48-61,共14页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by Hungarian National Research,Development and Innovation Fund Projects,No.GINOP-2.3.3-15-2016-00006;Hungarian NKFIH Fund Project,No.FK131789(to Bódi N);János Bolyai Research Scholarship of the Hungarian Academy of Sciences(to Bódi N);ÚNKP-21-5-New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research,Development and Innovation Fund(to Bódi N);Gedeon Richter Plc Centenary Foundation(to Bódi N).

摘　　要：BACKGROUND Cytokines are essential in autoimmune inflammatory processes that accompany type 1 diabetes.Tumor necrosis factor alpha plays a key role among others in modulating enteric neuroinflammation,however,it has a dual role in cell degeneration or survival depending on different TNFRs.In general,TNFR1 is believed to trigger apoptosis,while TNFR2 promotes cell regeneration.The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy,however,the expression and alterations of different TNFRs in the gastrointestinal tract has not been reported.AIM To investigate the TNFR1 and TNFR2 expression in myenteric ganglia and their environment in different intestinal segments of diabetic rats.METHODS Ten weeks after the onset of hyperglycemia,gut segments were taken from the duodenum,ileum and colon of streptozotocin-induced(60 mg/body weight kg i.p.)diabetic(n=17),insulin-treated diabetic(n=15)and sex-and age-matched control(n=15)rats.Myenteric plexus whole-mount preparations were prepared from different gut regions for TNFR1/HuCD or TNFR2/HuCD double-labeling fluorescent immunohistochemistry.TNFR1 and TNFR2 expression was evaluated by post-embedding immunogold electron microscopy on ultrathin sections of myenteric ganglia.TNFRs levels were measured by enzyme-linked immunosorbent assay in muscle/myenteric plexus-containing(MUSCLE-MP)tissue homogenates from different gut segments and experimental conditions.RESULTS A distinct region-dependent TNFRs expression was detected in controls.The density of TNFR1-labeling gold particles was lowest,while TNFR2 density was highest in duodenal ganglia and a decreased TNFRs expression from proximal to distal segments was observed in MUSCLE-MP homogenates.In diabetics,the TNFR2 density was only significantly altered in the duodenum with decrease in the ganglia(0.32±0.02 vs 0.45±0.04,P<0.05),while no significant changes in TNFR1 density was observed.In diabetic MUSCLE-MP homogenates,both TNFRs levels significantly dec

关 键 词：Tumor necrosis factor alpha receptors Myenteric ganglia Enteric neurons Neuronal environment Diabetes Insulin 

分 类 号：R574[医药卫生—消化系统]