Therapeutic role of miR-26a on cardiaorenal injury in mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated a microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t-test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS: Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.

Peanut skin procyanidins reduce intestinal glucose transport protein expression, regulate serum metabolites and ameliorate hyperglycemia in diabetic mice.

One of diabetic characteristics is the postprandial hyperglycemia. Inhibiting glucose uptake may be beneficial for controlling postprandial blood glucose levels and regulating the glucose metabolism Peanut skin procyanidins (PSP) have shown a potential for lowering blood glucose; however, the underlying mechanism through which PSP regulate glucose metabolism remains unknown. In the current study, we investigated the effect of PSP on intestinal glucose transporters and serum metabolites using a mouse model of diabetic mice. Results showed that PSP improved glucose tolerance and systemic insulin sensitivity, which coincided with decreased expression of sodium-glucose cotransporter 1 and glucose transporter 2 in the intestinal epithelium induced by an activation of the phospholipase C ß2/protein kinase C signaling pathway. Moreover, untargeted metabolomic analysis of serum samples revealed that PSP altered arachidonic acid, sphingolipid, glycerophospholipid, bile acids, and arginine metabolic pathways. The study provides new insight into the anti-diabetic mechanism of PSP and a basis for further research.

Improved photoredox activity of the 2D Bi4Ti3O12-BiVO4-Bi4V2O10 heterostructure via the piezoelectricity-enhanced charge transfer effect.

Introducing piezoelectric materials with the built-in electric field caused by mechanical force has been confirmed as an effective strategy to boost the separation efficiency of photoexcited charge carriers that determines the photocatalytic performance. In this study, we introduced Bi4Ti3O12 with superior piezoelectric properties into BiVO4-Bi4V2O10 materials to synthesize a 2D Bi4Ti3O12-BiVO4-Bi4V2O10 photocatalyst via a facile hydrothermal method. Compared with bare BiVO4, the Bi4Ti3O12-BiVO4-Bi4V2O10 piezo-photocatalytic activity towards Cr(VI) removal and oxygen evolution is boosted remarkably under both illumination and ultrasound treatments. The promoted photocatalytic activity can be ascribed to the accelerated photoexcited carrier separation efficiency driven by the polarization electric field and the synergy effect in the heterostructure. This work provides a simple and sustainable strategy for the design and development of piezo-photocatalysts with high photoredox activity capacity.

Expression profiles of long non-coding RNAs during fetal lung development.

With advances in neonatology, a greater percentage of premature infants now survive and consequently, diseases of lung development, including bronchopulmonary dysplasia and neonatal respiratory distress syndrome, have become more common. However, few studies have addressed the association between fetal lung development and long non-coding RNA (lncRNA). In the present study, right lung tissue samples of fetuses at different gestational ages were collected within 2 h of the induction of labor in order to observe morphological discrepancies. An Affymetrix Human GeneChip was used to identify differentially expressed lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. A total of 687 lncRNAs were identified to be differentially expressed among three groups of fetal lung tissue samples corresponding to the three embryonic periods. A total of 34 significantly upregulated and 12 significantly downregulated lncRNAs (fold-change, ≥1.5; P<0.05) were detected at different time points (embryonic weeks 7-16, 16-25 and 25-28) of fetal lung development and compared with healthy tissues Expression changes in lncRNAs n340848, n387037, n336823 and ENST00000445168 were validated by reverse transcription-quantitative PCR and the results were consistent with the GeneChip results. These novel identified lncRNAs may have roles in fetal lung development and the results of the present study may lay the foundation for subsequent in-depth studies into lncRNAs in fetal lung development and subsequent clarification of the pathogenesis of neonatal pulmonary diseases.

[Continuous expression of miR-431 during lung development in Sprague-Dawley rats].

OBJECTIVE: To study the role of miR-431 in lung development and morphology. METHODS: According to the stage of lung development in rats, Sprague-Dawley rats at embryonic day 16 (E16), embryonic day (E19), embryonic day (E21), postnatal day 1 (P1), postnatal day 3 (P3), postnatal day 7 (P7), postnatal day 14 (P14) and 10 weeks after birth (P10 weeks) were selected, and lung tissue samples were collected for observation. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe the morphology of lung tissue. Fluorescence in situ hybridization and real-time PCR were used to measure the expression of miR-431 during the critical stages of lung development (E19, E21 and P3). RESULTS: The E19 group had the formation of the lamellar body and type II alveolar epithelial cells in the fetal lung tissue. The number of lamellar bodies increased with the increasing gestational age, with aggregation and excretion. Pulmonary alveoli formed rapidly, the lung interstitium became thinner, and the microvascular system became mature after birth. Fluorescence in situ hybridization and real-time PCR showed that the expression of miR-431 gradually decreased with the increasing gestational age (P<0.05). CONCLUSIONS: The systematic and continuous morphological data of lung development is obtained in this experiment. In addition, miR-431 may play an important role in the negative regulation of lung development, which provides basis and direction for further research on the mechanism of lung development and related diseases.

Knockout of microRNA­26a promotes lung development and pulmonary surfactant synthesis.

Normal formation and function of the lungs are essential for the transition of the fetus to an air­breathing environment at birth. The synthesis of pulmonary surfactant (PS), which is produced by type II alveolar epithelial cells (AECIIs), is required for proper lung development. Previous in vitro studies have suggested that PS synthesis is regulated by microRNA (miR)­26a in fetal rat AECIIs. The present study explored the potential role of miR­26a in lung development and PS synthesis by using a miR­26a­1/miR­26a­2 double knockout mouse model. Hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of fetal lungs. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein levels of surfactant­associated proteins. The results demonstrated that the lung formation in the knockout mice was more mature, and that there were more mature lamellar bodies inside AECIIs in miR­26a knockout mice at late stages of lung development. The findings further demonstrated that knockout of miR­26a increased surfactant­associated mRNA and protein expression levels. The results indicated that knockout of miR­26a promotes lung development and PS synthesis.