Protective impacts of circular RNA VMA21 on lipopolysaccharide-engendered WI-38 cells injury via mediating microRNA-142-3p.

CircRNA derived from vacuolar ATPase assembly factor (circVMA21) is a newly-researched circRNA, which is reported to adjust the degeneration of intervertebral disc. But, function of circVMA21 in infantile pneumonia is yet to be explored. The research surveyed the role of circVMA21 in lipopolysaccharide (LPS)-caused WI-38 cell inflammatory injury. LPS (10 µg/ml, 12 hr) was exploited to arouse WI-38 cell inflammatory injury. Subsequently, the mediatory impacts of microRNA (miR)-142-3p and circVMA21 in LPS-evoked cell injury were detected after transfection with the inhibited or overexpressed vectors. In above processes, cell behaviors of cell viability, apoptosis, and pro-inflammatory factors were monitored. NF-κB and JNK pathways were elucidated to showcase the feasible molecular mechanisms. Results displayed that LPS engendered WI-38 cell inflammatory injury was alleviated as well as activated NF-κB and JNK pathways was interdicted by miR-142-3p suppression. Importantly, restrained miR-142-3p expression was discovered in WI-38 cells after overexpressing circVMA21. Moreover, overexpressed circVMA21 exerted the similar functions as miR-142-3p suppression in LPS-triggered WI-38 cell injury. But, the influence was clearly reversed by miR-142-3p overexpression. Hindered NF-κB and JNK pathways caused by overexpressed circVMA21 was also crippled by miR-142-3p overexpression. The research discolsed that circVMA21 protected WI-38 cells to resist LPS-triggered inflammatory injury via miR-142-3p-NF-κB/JNK axis.

Bao Yuan decoction and Tao Hong Si Wu decoction improve lung structural remodeling in a rat model of myocardial infarction: Possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-ß1/Smad3 and NF-κB pathways.

Chronic heart failure (CHF) leads to pulmonary structural remodeling, which may be a key factor for poor clinical outcomes in patients with end-stage heart failure, and few effective therapeutic options are presently available. The aim of the current study was to explore the mechanism of action and pulmonary-protective effects of treatment with Bao Yuan decoction combined with Tao Hong Si Wu decoction (BYTH) on lung structural remodeling in rats with ischemic heart failure. In a model of myocardial infarction (MI) induced by ligation of the left anterior descending (LAD) artery, rats were treated with BYTH. Heart function and morphometry were measured followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. The levels of transforming growth factor-ß1 (TGF-ß1), type I collagen, phosphorylated-Smad3 (p-Smad3), tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), active nuclear factor κB (NF-κB) and alpha smooth muscle actin (α-SMA) were detected using Western blotting. Lung weight increased after an infarct with no evidence of pulmonary edema and returned to normal as a result of BYTH. In addition, BYTH treatment reduced levels of type I collagen, TGF-ß1, and α-SMA expression and decreased the phosphorylation of Smad3 in the lungs of rats after MI. BYTH treatment also reduced the elevated levels of lung inflammatory mediators such as TNF-α, TLR4, and NF-κB. Results suggested that BYTH could effectively improve lung structural remodeling after MI because of its anti-inflammatory and anti-fibrotic action, which may be mediated by suppression of the TGF-ß1/Smad3 and NF-κB signaling pathways.

The effect of down-regulation of CCL5 on lipopolysaccharide-induced WI-38 fibroblast injury: a potential role for infantile pneumonia.

OBJECTIVES: Aberrant expression of CCL5 has been found in several kinds of inflammatory diseases, and the roles of CCL5 in these diseases have also been reported. However, the role of CCL5 in infantile pneumonia is still unclear. Thus, the function and acting mechanism of CCL5 in the in vitro model of infantile pneumonia were researched in this study. MATERIALS AND METHODS: Human fetal lung fibroblast WI-38 cells were subjected with lipopolysaccharide (LPS) to mimic an in vitro model of pneumonia. CCL5 was silenced by transfection with CCL5-targeted siRNA, and then cell viability, apoptosis, and the expressions of apoptosis-associated factors were respectively assessed by CCK-8 assay, flow cytometry and Western blot. Besides, expressions of CCL5 and pro-inflammatory factors were analyzed by qRT-PCR and Western blot. The secretions of pro-inflammatory factors were measured by ELISA. Finally, the expressions of main factors in JNK and NF-κB pathways were detected. RESULTS: LPS treatment suppressed cell viability, promoted cell apoptosis, and enhanced the secretion of IL-6, MCP-1, and TNF-α. Overexpression of CCL5 was found in LPS-treated cells. CCL5 silence protected WI-38 cells from LPS-induced inflammatory damage, with increasing cell viability, inhibiting cell apoptosis, and reducing the production of pro-inflammatory cytokines. Besides, CCL5 silence inhibited LPS-induced activations of JNK and NF-κB pathways. CONCLUSION: Down-regulation of CCL5 could protect WI-38 cells from LPS-induced inflammatory damage via inactivating JNK and NF-κB pathways.

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-ß1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction.

BACKGROUND/AIMS: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. METHODS: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-ß1 (TGF-ß1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. RESULTS: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-ß1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. CONCLUSIONS: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-ß1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

[Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Heart Failure Rats after Myocardial Infarction and Its Mechanism].

Objective To observe the effect of Qili Qiangxin Capsule (QQC) in improving lung struc- tural remodeling on heart failure (HF) rats after myocardial infarction (Ml) and to study its possible mecha- nism. Methods The proximal left anterior descending branch of coronary artery was ligated using a terylene suture to establish acute myocardial infarction (AMI) rat model. After successful AMI modeling rats were ran- domly divided into the model group (intragastrically administered with distilled water at 1 mL/100 g, n =13) and the QQC group (intragastrically administered with QQC at the daily dose of 1 g/kg, n =9). And the sham-opera- tion group (intragastrically administered with distilled water at 1 mL/100 g, n =10) was also set up. After four weeks intervention heart functions of rats were detected using echocardiography. The pathological changes of lung structures were observed by HE and Masson staining method. Protein expressions of lung α-SMA, Collagen I, TGF-ß1, and p-Smad3 of the lung tissue were detected by immunohistochemistry and Western blot. Re- sults Compared with the sham-operation group, ejection fraction (EF) and fraction shortening (FS) decreased (P <0. 05) , protein expressions of lung left ventricular internal diastolic diameter (LVIDd), left ventric- ular internal systolic diameter (LVIDs), end diastolic volume (EDV), end systolic volume (ESV), α-smooth muscle actin (a-SMA), Collagen I, tumor growth factor-ß1 (TGF-ß1), and p-Smad3 increased (P <0.05) in the model group. The muscularized small arteries ratio and collagen area of the lung tissue increased in the model group (P <0. 05). Compared with the model group, EF and FS increased (P <0. 05), protein expressions of LVIDs, ESV, α-SMA, Collagen I, TGF-ß, , and p-Smad3 decreased (P <0.05) in the QQC group. The muscular- ized small arteries ratio and collagen area of the lung tissue decreased in the QQC group (P <0. 05). Conclusion QQC could improve lung structural remodeling degree of HF rats after MI, and its possible mechanism might be achieved by regulating TGF-beta,/Smad3 signaling pathways.

Effects of Qili Qiangxin Capsule on AQP2, V2R, and AT1R in Rats with Chronic Heart Failure.

Qili qiangxin capsule (QL), a traditional Chinese herbal compound, has been proved to be effective and safe for the treatment of chronic heart failure (CHF). Upregulation of aquaporin-2 (AQP2) accounts for the water retention in CHF. The aim of the present study was to evaluate the effects of QL on the expression of AQP2 in rats with CHF induced by acute myocardial infarction and to investigate the underlying mechanisms. The urine output of all rats was quantified and collected every day at the first week and the 4th week after administration of QL or Valsartan. The expression of AQP2, vasopressin type 2 receptor (V2R), and angiotensin II type 1 receptor (AT1R) were examined after treatment for 4 weeks. Urinary output increased significantly after administration of QL. Importantly, the protein expression of AQP2 and AQP2 phosphorylated at serine 256 (pS256-AQP2) was downregulated after administration of QL and Valsartan to CHF rats. Furthermore, QL reduced plasma arginine vasopressin (AVP) and angiotensin II (AngII) level and downregulated V2R and AT1R protein expression. Thus, QL exerts its diuretic effect and improves cardiac function in CHF rats by reversing the increases in both AQP2 and pS256-AQP2 expression. The possible mechanisms may involve inhibition of V2R and AT1R.