LncRNA INPP5F ameliorates stress-induced hypertension via the miR-335/Cttn axis in rostral ventrolateral medulla.

AIMS: The rostral ventrolateral medulla (RVLM) is an essential vasomotor center responsible for regulating the development of stress-induced hypertension (SIH). Long non-coding RNAs (lncRNAs) play critical roles in various physiopathology processes, but existing research on the functions of RVLM lncRNAs on SIH has been lacking. In this study, we investigated the roles of RVLM lncRNAs in SIH. METHODS: Genome-wide lncRNA profiles in RVLM were determined by RNA sequencing in a SIH rat model established using electric foot shocks plus noises. The hypotensive effect of lncRNA INPP5F and the underlying mechanisms of lncRNA INPP5F on SIH were explored through in vivo and in vitro experiments, such as intra-RVLM microinjection and immunofluorescence. RESULTS: We discovered 10,179 lncRNA transcripts, among which the lncRNA INPP5F expression level was significantly decreased in SIH rats. Overexpression of lncRNA INPP5F in RVLM dramatically reduced the blood pressure, sympathetic nerve activity, and neuronal excitability of SIH rats. LncRNA INPP5F overexpression markedly increased Cttn expression and reduced neural apoptosis by activating the PI3K-AKT pathway, and its inhibition had opposite effects. Mechanistically, lncRNA INPP5F acted as a sponge of miR-335, which further regulated the Cttn expression. CONCLUSION: LncRNA INPP5F was a key factor that inhibited SIH progression, and the identified lncRNA INPP5F/miR-335/Cttn/PI3K-AKT/apoptosis axis represented one of the possible mechanisms. LncRNA INPP5F could serve as a therapeutic target for SIH.

Microcystin-LR exposure interfered maintenance of colonic microenvironmental homeostasis in rat.

Microcystin-leucine arginine (MCLR) is a phycotoxin produced by cyanobacteria. As a hepatotoxin, increasing evidence suggests that it has some negative effects on the mammal gastrointestinal tract, but further studies are warranted. In this study, we investigated the effects of MCLR on the intestinal epithelial microenvironment by oral administration of MCLR. As expected, MCLR at doses of 200 and 400 µg kg-1 bw showed hepatorenal toxicity in rats but without significant gastrointestinal symptoms. MCLR exposure decreased the thickness of the colonic epithelial mucus layer, and down-regulated the expression of main mucin protein (MUC2), cytoskeletal assembly-related genes (Arpc1a, Enah) and cytoskeletal stability-related genes (Ptk2, Prkca, Actn1, Pxn, Tln1, Cttn, Vcl) in colonic tissue to varying degrees, but did not affect the expression of cell connection-related genes including Zo1, Ocln, Cldn2 and Cdh1. In addition, MCLR exposure had a limited effect on gut bacterial diversity but clearly enriched specific bacteria. Prevotella, which plays a crucial role in balancing health and disease, was inhibited, whereas Muribaculaceae concerning the epithelial barrier, was promoted. Together, our findings demonstrate that MCLR exposure can weaken the colonic epithelial barrier by interfering with the stability of the cytoskeleton, which in turn exacerbates the homeostasis maintenance in the intestinal microenvironment.

Expression and clinical significance of cortactin protein in ovarian neoplasms

Objective. To examine the expression of cortactin in epithelial ovarian cancer, and discuss the relationship between the expression of cortactin and the clinical pathology characteristics in epithelial ovarian cancer, as well as clinical significance. Methods. The expression of cortactin was detected using real-time fluorescence quantitative PCR and immunohistochemical SP method in epithelial ovarian cancer. Results. (1) The relative content of cortactin mRNA in epithelial ovarian cancer tissue was higher than that in benign control tissue, and expression was related to histological classification and FIGO stage. (2) Cortactin protein was localized in the cytoplasm and membrane of tumor cells. The positive rate of cortactin was 73.3 % in epithelial ovarian cancer, and the rate of cortactin expression was related to histological classification. (3) The average survival period of epithelial ovarian cancer patients with positive expression of cortactin was 19.5 ± 1.2 months (95 % CI 14.6-21.4 months), compared with 34.5 ± 4.3 months in the negative expression group (95 % CI 22.1-25.9 months). Univariate survival analysis showed that: negative expression of cortactin had a significant survival advantage (χ 2 = 5.739, P = 0.017). A cox regression model for multivariate analysis revealed that cortactin was an independent prognostic factor for epithelial ovarian cancer (P = 0.001; RR = 6.452, 95 % CI 2.289-7.112). Conclusions. Negative expression of cortactin was an independent prognostic factor and had a survival advantage. This suggested that cells with poor differentiation showed increasing motility. Cortactin is closely related to poor prognosis (AU)

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A Hip1R-cortactin complex negatively regulates actin assembly associated with endocytosis.

Actin polymerization plays a critical role in clathrin-mediated endocytosis in many cell types, but how polymerization is regulated is not known. Hip1R may negatively regulate actin assembly during endocytosis because its depletion increases actin assembly at endocytic sites. Here, we show that the C-terminal proline-rich domain of Hip1R binds to the SH3 domain of cortactin, a protein that binds to dynamin, actin filaments and the Arp2/3 complex. We demonstrate that Hip1R deleted for the cortactin-binding site loses its ability to rescue fully the formation of abnormal actin structures at endocytic sites induced by Hip1R siRNA. To determine when this complex might function during endocytosis, we performed live cell imaging. The maximum in vivo recruitment of Hip1R, clathrin and cortactin to endocytic sites was coincident, and all three proteins disappeared together upon formation of a clathrin-coated vesicle. Finally, we showed that Hip1R inhibits actin assembly by forming a complex with cortactin that blocks actin filament barbed end elongation.