Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.

[1] We measured Vp/Vs ratios of thermally cracked Westerly granite, thermally cracked Carrara marble and 4% porosity Fontainebleau sandstone, for an effective mean pressure ranging from 2 to 95 MPa. Samples were fluidsaturated alternatively with argon gas and water (5 MPa constant pore pressure). The experimental results show that at ultrasonic frequencies, Vp/Vs ratio of water saturated specimen never exceeded 2.15, even at effective mean pressure as low as 2 MPa, or for a lithology for which the Poisson's ratio of minerals is as high as 0.3 (calcite). In order to check these results against theoretical models: we examine first a randomly oriented cracked medium (with dispersion but without anisotropy); and second a medium with horizontally aligned cracks (with anisotropy but without dispersion). The numerical results show that experimental data agree well with the first model: at high frequency, Vp/Vs ratios range from 1.6 to 1.8 in the dry case and from 1.6 to 2.2 in the saturated case. The second model predicts both Vp/Sv and Vp/Sh to vary from 1.2 to 3.5, depending on the raypath angle relative to the crack fabric. In addition, perpendicular to the crack fabric, a high Vp/Vs ratio is predicted in the absence of shear wave splitting. From these results, we argue the possibility that high Vp/Vs ratio (>2.2) as recently imaged by seismic tomography in subduction zones, may come from zones presenting important crack anisotropy. The cumulative effects of crack anisotropy and high pore fluid pressure are required to get Vp/Vs ratios above 2.2. Citation: