IncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch Schonlein purpura rats

Author(s):  
mingyu Jiang ◽  
Ji-cheng Dai ◽  
Ming-ying Yin ◽  
Ming-yong Ren

Abstract Background: Long noncoding RNAs (lncRNAs) are important regulatory molecules in various biological and pathological processes. We herein aimed to explore whether maternally expressed gene 8 (MEG8) promotes M1 macrophage polarization in Henoch-Schonlein purpura (HSP) rats and to investigate the underlying mechanism.Methods: Relative MEG8 and miR-181a-5p expression and suppressor of SH2 domain-containing tyrosine phosphatase 2 (SHP2) RNA level were examined using quantitative reverse transcription polymerase chain reaction. Expression of SHP2 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway-related proteins was detected using western blot. Luciferase activity assay was performed to test whether miR-181a-5p could bind to MEG8 or SHP2. The macrophage phenotype was determined using flow cytometry analysis and enzyme-linked immunosorbent assay.Results: The macrophage polarization toward the M2 phenotype was observed inperipheral blood from HSP rats. Furthermore, MEG8 and SHP2 expression were down-regulated but miR-181a-5p was up-regulated in monocyte-derived macrophages from HSP rats compared with the control group. Furthermore, MEG8 acted as a sponge for miR-181a-5p to facilitate SHP2 expression. Moreover, miR-181a-5p mimic and SHP2 knockdown significantly reversed the MEG8 overexpression-mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization.Conclusion: IncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch Schonlein purpura rats.

2021 ◽  
Vol 53 (1) ◽  
pp. 1576-1588
Author(s):  
Mingyu Jiang ◽  
Jicheng Dai ◽  
Mingying Yin ◽  
Chunming Jiang ◽  
Mingyong Ren ◽  
...  

2020 ◽  
Author(s):  
Qingyin Guo ◽  
Xiaolei Hu ◽  
Chundong Song ◽  
Xianqing Ren ◽  
Wensheng Zhai ◽  
...  

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.


2021 ◽  
Author(s):  
Jin-Kun Wang ◽  
Yan Bo ◽  
Qi-lian Zhou ◽  
Li-ping Yuan

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.


Author(s):  
Yuanzhen Zhang ◽  
Guizhi Xia ◽  
Xiaojing Nie ◽  
Yugui Zeng ◽  
Yi Chen ◽  
...  

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).


2019 ◽  
Vol 6 (4) ◽  
pp. 221-225
Author(s):  
K. Chaika ◽  
N. Makieieva

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.  


2021 ◽  
pp. jim-2021-001984
Author(s):  
Li Wang ◽  
Chunyan Yin ◽  
Meizhen Zhang ◽  
Hua Mao ◽  
Huixiang Hao ◽  
...  

The amino acid-based formulae were extensively added to diet of children for the treatment of Henoch-Schonlein purpura (HSP), and the nutrition and growth situation of children were evaluated after giving new dietary intervention. Patients were randomly divided into restricted diet group (n=30) and dietary guidance group (n=30). Besides, 30 cases with bronchiolitis who had normal diet were selected as the control group. The dietary questionnaire was designed to record the types and intakes of various foods taken by children every day, and the intake levels of nutrients were analyzed. Physical examination, biochemical analysis of blood and urine routine were carried out to evaluate the effect of dietary guidance on their growth and development. The results showed that restricted diet group had lower levels of nutrient intake and the actual/recommended percentage. However, overall nutrient intake level of the dietary guidance group was higher, basically equal to the recommended intake level. Besides, the actual intake and actual/recommended percentage of nutrients of dietary guidance group were significantly higher than those of restricted diet group (p<0.05). Dietary guidance can improve nutrients and protein intake of children with HSP, and reduce the relapse of rash and incidence of complications.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Li Wu ◽  
Jianhua Mao ◽  
Xia Jin ◽  
Haidong Fu ◽  
Huijun Shen ◽  
...  

Objective.To observe the clinical efficacy of the Chinese herb, Triptolide, in children with moderately severe Henoch-Schönlein purpura nephritis (HSPN).Methods. From January 2007 to December 2011, 56 HSPN children manifested by nephrotic range proteinuria with normal kidney function and<50% crescents or sclerosing lesions on biopsy were hospitalized in the Children’s Hospital of Zhejiang University School of Medicine. They were divided into two groups: the treatment group (Triptolide at a dosage of 1 mg/kg·d, combined with prednisone at a dosage of 2 mg/kg·d, within a course of medium-to-long-term therapy of 6 to 9 months) and the control group (; prednisone alone, with the same procedure).Results.Short-term remission was observed in 95% of patients from treatment group and in 72% of patients from control group, respectively. There was a significant difference between both groups () for short-term effects. Meanwhile, no significant difference, as proteinuria, hematuria, hypertension, and decreased eGFR, was observed between the two groups in long-term followup (). The Kaplan-Meier plot analysis also revealed no significant difference ().Conclusion.Triptolide is effective in relieving short-term symptoms for moderately severe HSPN children, though its long-term effects need to be observed further.


2021 ◽  
Vol 38 (1) ◽  
Author(s):  
Chao Li ◽  
Zhi-bin Wang

Objectives: To investigate the curative effect of Compound Glycyrrhizin Tablets in the adjuvant treatment of simplex Henoch-Schonlein purpura and its influence in improving immune function. Methods: In this retrospective study design was used in this study. Eighty newly diagnosed patients with purpura simplex who visited the outpatient department of Baoding First Central Hospital from June 2017 to February 2020 were included. They were randomly divided into treatment group and control group. The two groups were provided with the same conventional comprehensive treatment. Patients in the treatment group received oral administration of Compound Glycyrrhizin Tablets on the basis of conventional treatment. The clinical efficacy of the treatment group and the control group were compared according to the time and effect of purpura regression, followed by the comparison of changes of T cell subsets before and after treatment. Results: The total effective rate of the treatment group was 92.5%, which was higher than that of the control group (77.5%) (P < 0.05). The purpura subsidence time of effective patients in treatment group was shorter than that in control group (P < 0.05). There was no significant difference in lymphocyte subsets between the treatment group and the control group before treatment. After treatment, the proportion of CD4+ cells and CD4+/CD8+ cells in the treatment group were obviously higher than that in the control group, and the count of CD8+ cells was evidently lower than that in the control group (P < 0.05). Conclusions: Compound Glycyrrhizin is effective in the adjuvant treatment of simplex Henoch-Schonlein purpura without obvious adverse reactions, which is valuable for clinical application as an adjuvant. doi: https://doi.org/10.12669/pjms.38.1.4609 How to cite this:Li C, Wang Z. Clinical application of compound Glycyrrhizin tablets in the treatment of patients with Simplex Henoch-Schonlein Purpura and its effect on immune function. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4609 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2020 ◽  
Author(s):  
Xianhe Wang ◽  
Man Wu ◽  
Yan Liu ◽  
Hui Gao ◽  
Fang Deng

Abstract BackgroundDuring the development of Henoch-Schönlein purpura nephritis (HSPN), the activation and overexpression of transient receptor potential cation channel protein 6 (TRPC6) and the activation of Nod-like receptor protein 3 (NLRP3) inflammasome play a very important role. However, whether the expression of TRPC6 in children with HSPN is related to the activation of NLRP3 inflammasome has not been reported.MethodsWe obtained kidney biopsy specimens of 33 children with HSPN and 6 controls with renal trauma. Immunohistochemistry was used to detect the expression of TRPC6, NLRP3, ASC, caspase-1, IL-1β, IL-18. Student’s t-test was used to analyze the difference between the HSPN and control group. Pearson correlation test was used to estimate the correlation between TRPC6 and NLRP3 inflammasome among HSPN children. A bootstrap approach was performed for mediation effects of NLRP3 inflammasome on the association between TRPC6 and HSPN.ResultsThe expressions of TRPC6, NLRP3, ASC, Caspase-1, IL-1β, IL-18 in kidney tissues of children with HSPN were significantly higher than those in the control group (all P values <0.05). Significant correlations of TRPC6 with NLRP3, ASC, and IL-18 were observed. NLRP3 and ASC were also related to the levels of IL-1β and IL-18. Significant mediation effects (0.08, 95%CI = 0.04-0.15) of ASC on the association between TRPC6 and HSPN was revealed, with explaining 58.25% of the total effects.ConclusionTRPC6 may cause the release of IL-1β and IL-18 by activating the NLRP3 inflammasome, especially the expression of ASC, thereby damaging the kidneys of children with HSP.


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