The present study aimed to determine whether isorhamnetin (Isor), a natural antioxidant polyphenol, has antifibrotic effects in a murine model of bleomycin-induced pulmonary fibrosis. A C57 mouse model of pulmonary fibrosis was established by intraperitoneal injection of a single dose of bleomycin (3.5 U/kg), and then Isor (10 and 30 mg/kg) was administered intragastrically. The level of fibrosis was assessed by hematoxylin and eosin and Sirius red staining. α-smooth muscle actin and type I collagen levels in lung tissues were determined by western blotting and immunohistochemistry (IHC). Epithelial-mesenchymal transition (EMT), endoplasmic reticulum stress (ERS) and related signaling pathways were examined by western blotting and IHC. In vitro, human bronchial epithelial cells (HBECs) and A549 cells were treated with transforming growth factor (TGF)β1 with or without Isor, and collagen deposition and the expression levels of EMT- and ERS-related genes or proteins were analyzed by reverse transcription-quantitative polymerase chain reaction, western blotting, and immunofluorescence. The results demonstrated that Isor inhibited bleomycin-induced collagen deposition, reduced type I collagen and α-SMA expression, and alleviated EMT and ERS in vivo. Furthermore, incubation of HBECs and A549 cells with TGFβ1 activated EMT and ERS, and this effect was reversed by Isor. In conclusion, Isor treatment attenuated bleomycin-induced EMT and pulmonary fibrosis and suppressed bleomycin-induced ERS and the activation of PERK signaling.
BackgroundMatrix mineralization is a key stage in bone formation involving in many bone-specific genes and signaling pathways. Emerging evidence indicate that long non-coding RNA (lncRNA) and microRNAs (miRNAs) play crucial roles in regulating the mineralization process of osteoblasts. This study aims to characterize the function and mechanism of lncRNA H19/miR-185-5p/IGF1 axis in modulating matrix mineralization of osteoblasts.ResultsH19 and IGF1 were highly expressed while miR-185-5p was lowly expressed in mineralized cells. Knocking down H19 inhibited matrix mineralization of osteoblasts, yet miR-185-5p had opposite effects. Moreover, H19 directly targeted miR-185-5p, whereas miR-185-5p repressed IGF1 expression. Meanwhile, miR-185-5p inhibition compensated the suppression of the matrix mineralization in osteoblasts by H19 knockdown.ConclusionsThe findings of this study showed that lncRNA H19 was upregulated in mineralized osteoblasts and promoted matrix mineralization through miR-185-5p/IGF1 axis in osteoblasts for the first time. This study may provide a new perspective for the diagnosis and treatment of diseases related to bone metabolism.
Atherosclerotic cardiovascular diseases, such as coronary heart disease, have become a major public health problem all over the world. MicroRNA-29a (miR-29a) modulates expression levels of collagen, inflammatory reaction and other extracellular matrix mRNAs, while adiponectin (APN), a circulating protein secreted by adipocytes, has anti-inflammatory properties. Both play multifaceted roles in angiogenesis or vascular remodelling. However, little is known about plasma miR-29a and APN levels in patients with atherosclerosis. We therefore investigated the relationship between the plasma levels of miR-29a or APN and carotid intima-media thickness (cIMT) in atherosclerosis patients (n = 85, cIMT ≥ 1.2 mm) and the controls (n = 85, cIMT < 1.2 mm). We found that the atherosclerosis group showed higher miR-29a levels (31.15 ± 3.99 vs. 26.39 ± 1.05 Ct, P < 0.001) and lower APN levels (15.93 ± 4.61 vs. 21.80 ± 7.74 ng/ml, P < 0.001), compared with control group. Thus, increased cIMT was associated with higher plasma miR-29a levels (r = 0.688, P < 0.001) and with lower plasma APN levels (r = −0.494, P < 0.001). Furthermore, multiple logistic regression analysis indicated that higher miR-29a levels (OR: 1.136, 95% CI: 1.042-1.240, P = 0.004) increased the risk for atherosclerosis, whereas higher APN levels appeared to be protective (OR: 0.122, 95% CI: 0.055-0.271, P < 0.001). The present study indicates that elevated miR-29a levels and reduced APN levels are associated with atherosclerosis.Keywords: adiponectin; atherosclerosis; carotid intima-media thickness; microRNA; miR-29a Tohoku J. Exp. Med., 2017 March, 241 (3), 183-188. © 2017 Tohoku University Medical Press IntroductionAtherosclerotic cardiovascular diseases such as coronary heart disease and stroke have become a major public health problem all over the world (Murray et al. 2012). It is necessary to detect atherosclerotic cardiovascular diseases at earlier stages. In recent decades, microRNAs (miRs) are short non-coding RNA able to bind specific sequences on target mRNAs, thereby modulating gene expression (Gaudet and Brisson 2015). They are involved in almost every aspect of cellular or biological processes, and dysregulation of miRs correlated with cardiovascular diseases, such as atherosclerosis ). MiR-29a was one of the members of the miR-29 family (Hysolli et al. 2016). The miR-29 family, modulating mRNA level of collagen, inflammatory reaction and other extracellular matrix genes, play a multifaceted role in tissue remodelling and vessels injury Bretschneider et al. 2016). It was reported that miR-29 were up-regulated in the region of the heart adjacent to a myocardial infarction (MI) (van Rooij et al. 2008). Among other miRs, circulating miR-29a levels may represent one of the new biomarkers which significantly correlate with cardiovascular diseases (Roncarati et al. 2014). In addition, a previous study showed that miR-29b was involved in vascular smooth muscle cell migration and proliferation by mediating an epigenetic mechanism (Chen et al. 2011), which wa...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.