scholarly journals Involvement of Acid-Sensing Ion Channel 1a Contribute to The Effect of Extracellular Acidosis on Vascular Endothelialcell Damage of Henoch-Schönlein Purpura Patients

2021 ◽  
Author(s):  
Jin-Kun Wang ◽  
Yan Bo ◽  
Qi-lian Zhou ◽  
Li-ping Yuan
Keyword(s):  
Endothelial Cells ◽  
Ion Channel ◽  
Binding Activity ◽  
Control Group ◽  
Vascular Endothelial ◽  
Henoch Schonlein Purpura ◽  
Protein Expressions ◽  
Cytoskeleton Protein ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

Abstract Introduction: Henoch-Schönlein purpura (HSP) is a common kind of systematic vasculitis in children characterized by rash, joint pain,abdominal symptoms and renal disease,the detail pathogenesis of HSP has not been elucidated.Acid-sensing ion channels (ASICs) is a proton-gated sodium selective channel that belongs to Degenerin /epithelial Sodium Channel(DEG/ENaC) superfamily,previous research found the expression of ASIC1a in vascular endothellial cells could be stimulated by serum IgA1 from HSP patients under acidic environment.This study aims to investigate the molecular mechanisms of silencing of acid-sensing ion channel 1a(ASIC1a) protects the vascular endothelial cells from Henoch-Schonlein purpura(HSP) patients.Methods:Human dermal microvascular endothelial cells ( HDMVEC) were cultured in vitro，siRNA sequences were designed for the coding region of human ASIC1a gene and HDMVEC cells were transfected with recombinant lentivirus( LV) -sh-ASIC1a． The control group ( NC group) without virus transfection and LV-sh-ASIC1a transfection group ( si-ASIC1a group) were set up． The expression of transfixed ASIC1a gene was detected by RT-PCR． After virus transfection 72 h，serum IgA1from HSP patients and serum IgA1 of normal children were added into HDMVEC cells． ASIC1a and cytoskeleton protein ( sm-α f-actin，MLCK) mRNA and protein expressions were detected by real-time PCR and Western blotting Methods.The binding activity of NF- κB with DNA in HDMVEC was determined by electrophoretic mobility shift assay (EMSA).The whole-cell patch-clamp technique was used to record the current changes and electrophysiological characteristics of ASICs and calcium in HDMVEC.Results：Cytoskeleton protein ( sm-α f-actin，MLCK) mRNA and protein expressions in the group of si-ASIC1a group were significantly increased compared with the NC control group( P ＜ 0． 01) ．The HSP serum and silencing of ASIC1a had no significant effect on the binding activity of NF-κB with DNA in HDMVEC. Compared with the NC control group, the ASICS current and calcium overload of the si-ASIC1A group were reduced( P ＜ 0． 01) ．Conclusion: Silencing ASIC1a can protect HSP vascular endothelial cell injury by inhibiting ASIC1-related calcium influx and reducing the overload of calcium ,not the NF- κB signaling pathway.

scholarly journals Involvement of Acid-Sensing Ion Channel 1a Contribute to The Effect of Extracellular Acidosis on Vascular Endothelialcell Damage of Henoch-Schönlein Purpura Patients

2020 ◽  
Author(s):  
Jin-Kun Wang ◽  
Yan Bo ◽  
Qi-lian Zhou ◽  
Li-ping Yuan
Keyword(s):  
Endothelial Cells ◽  
Ion Channel ◽  
Vascular Endothelial Cells ◽  
Binding Activity ◽  
Control Group ◽  
Vascular Endothelial ◽  
Henoch Schonlein Purpura ◽  
Protein Expressions ◽  
Cytoskeleton Protein ◽  
Schonlein Purpura

Abstract Background: Henoch-Schönlein purpura (HSP) is a common kind of systematic vasculitis in children characterized by rash, joint pain,abdominal symptoms and renal disease,the detail pathogenesis of HSP has not been elucidated.Acid-sensing ion channels (ASICs) is a proton-gated sodium selective channel that belongs to Degenerin /epithelial Sodium Channel(DEG/ENaC) superfamily,previous research found the expressions of ASIC1a and ASIC3 in the vascular endothelial cells of HSPThis study aims to investigate the molecular mechanisms of silencing of acid-sensing ion channel 1a(ASIC1a) protects the vascular endothelial cells from Henoch-Schonlein purpura(HSP) patients.Findings:Human dermal microvascular endothelial cells ( HDMVEC) were cultured in vitro, siRNA sequences were designed for the coding region of human ASIC1a gene and HDMVEC cells were transfected with recombinant lentivirus( LV) -sh-ASIC1a. The control group ( NC group) without virus transfection and LV-sh-ASIC1a transfection group ( si-ASIC1a group) were set up. The expression of transfixed ASIC1a gene was detected by RT-PCR. After virus transfection 72 h, serum IgA1from HSP patients and serum IgA1 of normal children were added into HDMVEC cells. ASIC1a and cytoskeleton protein ( sm-α f-actin, MLCK) mRNA and protein expressions were detected by real-time PCR and Western blotting Methods.The binding activity of NF- κB with DNA in HDMVEC was determined by electrophoretic mobility shift assay (EMSA).The whole-cell patch-clamp technique was used to record the current changes and electrophysiological characteristics of ASICs in HDMVEC.Cytoskeleton protein ( sm-α f-actin, MLCK) mRNA and protein expressions in the group of si-ASIC1a group were significantly increased compared with the NC control group( P＜0.01). The HSP serum and silencing of ASIC1a had no significant effect on the binding activity of NF-κB with DNA in HDMVEC. Compared with the NC control group, the ASICS current and calcium overload of the si-ASIC1A group were reduced( P＜0.01) ．Conclusions: Silencing ASIC1a can protect HSP vascular endothelial cell injury by inhibiting ASIC1-related calcium influx and reducing the overload of calcium ,not the NF- κB signaling pathway.

scholarly journals Clinical Characteristics and Risk Factors of Gastrointestinal Perforation in Children with Henoch-Schönlein Purpura

2020 ◽  
Author(s):  
Qingyin Guo ◽  
Xiaolei Hu ◽  
Chundong Song ◽  
Xianqing Ren ◽  
Wensheng Zhai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Abdominal Pain ◽  
Intestinal Perforation ◽  
Renal Damage ◽  
Gastrointestinal Perforation ◽  
Small Vessel Vasculitis ◽  
Control Group ◽  
Henoch Schonlein Purpura ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

Abstract Background: Henoch-Schönlein purpura (HSP) is a common small vessel vasculitis in children. Gastrointestinal perforation (GP) rarely presents as a complication of HSP and was not well characterized. This study aimed to investigate the clinical features, diagnosis and risk factors of GP in children with HSP. Methods: We retrospectively reviewed the clinical data of 10791 children with HSP who attended our hospital between January 2014 and June 2018 and analyzed the treatment and clinical risk factors of 11 children with HSP complication with GP. Results: GP occurred in 11 children with HSP, with an incidence of 0.10%. Among the 11 cases HSP with GP, 1 case was gastric perforation and 10 cases were intestinal perforation. CT indicates perforation but ultrasonography did not indicate perforation in 5 cases of GP patients. The average duration of abdominal pain in HSP with GP was 9.3 days, and 9 cases (81.8%) with a duration of abdominal pain over 7 days. 3 cases of HSP with GP were treated by gastric/intestinal perforation repair and the other 8 cases were treated by enterectomy. The type of purpura, abdominal pain lasting more than 7 days, hematochezia, renal damage, and methylprednisolone dose more than 2mg/kg in GP with HSP patients show statistically significant compared with the control group (P<0.05). Conclusion: The incidence rate of GP in children with HSP was 0.10%. Abdominal (or mixed) HSP, hematochezia, renal damage, abdominal pain lasting more than 7 days, and methylprednisolone dose more than 2mg/kg may increase the risk of GP in children with HSP. CT has a high sensitivity for the diagnosis of GP. Early diagnosis and timely treatment of HSP with GP were very important for good clinical outcomes.

scholarly journals Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuanzhen Zhang ◽  
Guizhi Xia ◽  
Xiaojing Nie ◽  
Yugui Zeng ◽  
Yi Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Complement C3 ◽  
Control Group ◽  
Healthy Children ◽  
Microbiota Composition ◽  
Henoch Schonlein Purpura ◽  
Abdominal Symptoms ◽  
Schonlein Purpura ◽  
Gut Microbiota Composition ◽  
Henoch Schönlein Purpura

BackgroundGut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP.Methods16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children.ResultsThe diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement.ConclusionsThe gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).

scholarly journals PROINFLAMMATORY CYTOKINES IL-8 AND TNFα WITH HENOCH-SCHONLEIN PURPURA IN CHILDREN

2019 ◽  
Vol 6 (4) ◽  
pp. 221-225
Author(s):  
K. Chaika ◽  
N. Makieieva
Keyword(s):  
Proinflammatory Cytokines ◽  
Systemic Vasculitis ◽  
Control Group ◽  
Henoch Schonlein Purpura ◽  
Acute Period ◽  
Tnf Α ◽  
Significant Difference ◽  
Α Level ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

PROINFLAMMATORY CYTOKINES IL-8 AND TNFα IN HENOCH-SCHONLEIN PURPURA IN CHILDREN Chaika K., Makieieva N. Henoch-Schonlein purpura (HSP) belongs to a group of systemic vasculitis with predominant damage to small caliber vessels (EULAR/Pres, 2006). Difficulties in diagnosis in the early stages and the likelihood of developing complications leaves HSP in the top of the current issues of pediatrics today. Kidney damage is observed in 20-50% of patients with HSP and leads to complications. In recent years, the question of prognostic markers of progression of HSP remains open. The study involved examination of total of 83 HSP patients aged between 2 and 17, divided into two groups: patients with HSP without nephrotic syndrome (HSPWN, n = 58.35 of which were boys and 23 - girls) and a group of patients with HSP with renal syndrome (HSPN, n = 25.14 of them boys and 11 girls) in acute and remission periods. The Kraskal-Wallis analysis recorded a highly statistically significant H criterion for IL-8 in the acute period (H = 17.421, p = 0.0002) and the remission period (H = 13.035, p = 0.0015). IL-8 levels in both groups of patients with HSP WN and HSPN were significantly higher in the acute period than in the control group, and the difference was statistically significant (p = 0.0004 and p = 0.0002, respectively). No significant difference was found between the medians in both periods regarding TNF-α level (H = 4.136, p = 0.1264; H = 0.133, p = 0.9356). In the group HSPN in the acute phase, a high IL-8 level in serum has been recorded compared to the group HSPWN. There was no significant difference in TNF-α level in both groups. Keywords: children, Henoch-Schonlein purpura, Ig-A vasculitis, nephritis.   Абстракт ПРОЗАПАЛЬНІ ЦИТОКІНИ IL-8 ТА TNFα У ДІТЕЙ ІЗ ПУРПУРОЮ ШЕНЛЯЙН-ГЕНОХА Чайка Х., Макєєва H. Пурпура Шенлейна-Геноха (ПШГ) відноситься до групи системних васкулітів з переважним пошкодженням судин малого калібру (EULAR / Pres, 2006). Труднощі в діагностиці на ранніх стадіях та ймовірність розвитку ускладнень залишають ПШГ в числі актуальних проблем педіатрії сьогодні. Ураження нирок спостерігається у 20-50% пацієнтів з ПШГ і призводить до ускладнень. В останні роки питання прогностичних маркерів прогресування ПШГ залишається відкритим. Обстежено 83 пацієнта з ПШГ у віці від 2 до 17 років, які були розділені на дві групи: пацієнти з ПШГ без нефротичного синдрому (ПШГБН, n = 58, 35 з яких були хлопчики і 23 - дівчатка) і група пацієнтів із ПШГ з нирковим синдромом (ПШГН, n = 25, з них 14 хлопчиків і 11 дівчаток) в періоди загострення і ремісії. Аналіз Краскала-Уолліса зареєстрував високий статистично значимий критерій H для IL-8 в гострому періоді (H = 17,421, p = 0,0002) і періоді ремісії (H = 13,035, p = 0,0015). Рівні IL-8 в обох групах пацієнтів з ПШГБН і ПШГН були значно вище в гострому періоді, ніж у контрольній групі, і різниця була статистично значущою (p = 0,0004 і p = 0,0002, відповідно). Не було виявлено суттєвих відмінностей між медіанами в обидва періоди щодо рівня TNF-α (H = 4,136, p = 0,1264; H = 0,133, p = 0,9356). У групі ПШГН в гострій фазі був зафіксований високий рівень IL-8 в сироватці в порівнянні з групою ПШГБН. Не було значної різниці в рівні TNF-α в обох групах. Ключові слова: Ig-A васкуліт, діти, пурпура Шенлейна-Геноха, нефрит.   Абстракт ПРОВОСПАЛИТЕЛЬНЫЕ ЦИТОКИНЫ IL-8 И TNFα У ДЕТЕЙ С ПУРПУРОЙ ШЕНЛЕЙН-ГЕНОХА Чайка K., Макеева H. Пурпура Шенлейн-Геноха (ПШГ) относится к группе системных васкулитов с преимущественным повреждением сосудов малого калибра (EULAR / Pres, 2006). Трудности в диагностике на ранних стадиях и вероятность развития осложнений оставляют ПШГ в числе актуальных проблем педиатрии сегодня. Поражение почек наблюдается у 20-50% пациентов с ПШГ и приводит к осложнениям. В последние годы вопрос о прогностических маркерах прогрессирования ПШГ остается открытым. Обследовано 83 пациента с ПШГ в возрасте от 2 до 17 лет, которые были разделены на две группы: пациенты с ПШГ без нефротического синдрома (ПШГБН, n = 58, 35 из которых были мальчики и 23 - девочки) и группа пациенты с ПШГ с почечным синдромом (ПШГН, n = 25, из них 14 мальчиков и 11 девочек) в периоды обострения и ремиссии. Анализ Краскала-Уоллиса зарегистрировал высокий статистически значимый критерий H для IL-8 в остром периоде (H = 17,421, p = 0,0002) и периоде ремиссии (H = 13,035, p= 0,0015). Уровни IL-8 в обеих группах пациентов с ПШГБН и ПШГН были значительно выше в остром периоде, чем в контрольной группе, и разница была статистически значимой (p = 0,0004 и p = 0,0002, соответственно). Не было обнаружено существенных различий между медианами в оба периода в отношении уровня TNF-α (H = 4,136, p = 0,1264; H = 0,133, p = 0,9356). В группе ПШГН в острой фазе был зафиксирован высокий уровень IL-8 в сыворотке по сравнению с группой ПШГБН. Не было значительного различия в уровне TNF-α в обеих группах. Ключевые слова: Ig-A васкулит, дети,пурпура Шенлейн-Геноха, нефрит.  

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