shRNA-Induced Knockdown of a Bioinformatically Predicted Target IL10 Influences Functional Parameters in Spontaneously Hypertensive Rats with Asthma

Abstract

One of the most common comorbid pathology is asthma and arterial hypertension. For experimental modeling of comorbidity we have used spontaneously hypertensive rats with ovalbumin (OVA)-induced asthma. Rats were randomly divided into three groups: control group, OVA-induced asthma group; OVA-induced asthma + IL10 shRNA interference group. Target gene (IL10) was predicted by ANDSystem. We have demonstrated that RNA-interference of IL10 affected cardiovascular (tested using Millar microcatheter system) as well as respiratory functions (tested using force-oscillation technique, Flexivent) in rats. We have shown that during RNA-interference of IL10 gene in vivo there were changes in both cardiac and lung function parameters. These changes in the cardiovascular parameters can be described as positive. But the more intensive heart workload can lead to exhaust and decompensation of the heart functions. Knockdown of IL10 gene in asthma modeling induces some positive changes in respiratory functions of asthmatic animals such as decreased elastance and increased compliance of the lungs, as well as less pronounced pathomorphological changes in the lung tissue. Thus, we provide the data about experimentally confirmed functionality changes of the target which was in silico predicted to be associated with both asthma and hypertension – in our new experimental model of comorbid pathology.

Risk factor analysis and nomogram for predicting poor symptom control in smoking asthmatics

“…Another possible explanation may be that the comorbidities of interest in this study are intricately linked to the prognosis of asthma and display some common pathogenic mechanisms. For example, asthma, allergic rhinitis and sinusitis are all related to allergen exposure, with airway hyperresponsiveness, eosinophilia and upper airway remodeling [36][37][38]; smoking-asthma is non-Th2 type asthma [25], IL-17-neutrophil axis, foam cells, mast cells are involved in the development of non-Th2 type asthma, hypertension, atherosclerosis [39][40][41][42][43], and there is even a strong gene overlap between these diseases [44,45]; treatment of OSAS can improve asthma symptoms, which may be related to increased neutrophil airway inflammation in OSAS patients and airway hyperresponsiveness caused by pharyngeal collapse to vagal nerve stimulation [46,47]; GERD may induce asthma by increasing vagus nerve excitability, gastric reflux into the airways causing airway hyperresponsiveness, altering the airway microenvironment and altering epithelial gene expression [47][48][49], smoking may induce or exacerbate gastroesophageal reflux, and the two complement each other. In conclusion, an in-depth study of the relationship between asthma and the comorbidities with which it shares a common pathogenic mechanism may be a new idea for the development of novel drugs for asthma.…”

Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke

“…After purification, the virus titer was determined by real-time PCR (1.4×10 12 V. g/ml). The short hairpin RNA (shRNA) sequence complementary to the site on IL-10 mRNA was designed using the siDESIGN center (Dharmacon, Horizon Discovery Group Co) on a computer, which has been verified and used by researchers [ 24 ]. We chose GFAP as the promoter of miR-30-based shRNA cassettes, and the red fluorescent label of mCherry was connected, a plasmid which can target and interfere with the synthesis of IL-10 by astrocytes was synthesized, and it was named HBAAV2/9-GFAP-mir30-r-IL-10-mCherry.…”

Genetics of "atopic march" syntropy

“…Например, ассоциированный с астмой и атопическими заболеваниями регион 17q21, где располагаются гены, кодирующие гасдерминдомен-содержащие белки (GSDMA, GSDMB) и белок-регулятор биосинтеза сфинголипидов (ORMDL3), в значительной степени связан с другими иммунными заболеваниями, включая ревматоидный артрит, болезнь Крона и сахарный диабет [39,40]. Среди генов, оказывающих выраженное влияние на фенотипическую корреляцию астмы и артериальной гипертензии, присутствуют напрямую задействованные в развитии окислительного стресса, нарушениях иммунного ответа и неоваскуляризации, в частности гены CAT, IL10, TLR4, ANG/ RNASE4 [41][42][43][44]. Кроме того, некоторые антигипертензивные препараты могут спровоцировать приступ астмы, тогда как некоторые противоастматические лекарства могут ухудшить течение гипертонии.…”