Experimental study of the protective effects of SYVN1 against diabetic retinopathy

Abstract

Genetic factors play an important role in the pathogenesis of diabetic retinopathy (DR). While many studies have focused on genes that increase susceptibility to DR, herein, we aimed to explore genes that confer DR resistance. Previously, we identified Hmg CoA reductase degradation protein 1 (SYVN1) as a putative DR protective gene via gene expression analysis. Transgenic mice overexpressing SYVN1 and wild-type (WT) mice with streptozotocin-induced diabetes were used in this experiment. Retinal damage and vascular leakage were investigated 6 months after induction of diabetes by histopathological and retinal cell apoptosis analyses and by retinal perfusion of fluorescein isothiocyanate-conjugated dextran. Compared with diabetic WT mice, diabetic SYVN1 mice had significantly more cells and reduced apoptosis in the retinal ganglion layer. Retinal vascular leakage was significantly lower in diabetic SYVN1 mice than in diabetic WT mice. The expression levels of endoplasmic reticulum (ER) stress-related, pro-inflammatory, and pro-angiogenic genes were also analyzed. Lower expression levels were observed in diabetic SYVN1 mice than in WT controls, suggesting that SYVN1 may play an important role in inhibiting ER stress, chronic inflammation, and vascular overgrowth associated with DR. Thus, these results strongly supported our hypothesis that SYVN1 confers DR resistance.

LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a vital role in proliferation, apoptosis and autophagy in osteoarthritis

“…Synoviolin 1 (SYVN1) was associated with ER stress, chronic inflammation, and vascular overgrowth in diabetic retinopathy (DR) [37,38]. Overexpression of miR-125b-5p was associated with the pathogenesis of osteoarthritis by down-regulation of SYVN1 [38], reflecting that SYVN1 was closely associated with OA.…”

Insulin Promotes Corneal Nerve Repair and Wound Healing in Type 1 Diabetic Mice by Enhancing Wnt/β-Catenin Signaling

“…injection of streptozotocin (Sigma-Aldrich, St. Louis, MO), as previously described. 37 In the control group, a citric acid buffer solution was intraperitoneally injected into age-matched C57BL/6J mice. Follow-up tests showed that the blood glucose levels in diabetic mice were !16.7 mmol/L after 6 months.…”

“…Western blotting was performed as previously described. 37 Total protein was extracted from lysing mouse corneal epithelium samples and cultured TKE2 cells in radioimmunoprecipitation assay buffer. Protein quantification was performed using a kit (P0010; Beyotime Biotechnology, Beijing, China).…”

Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis

“…MAOB (monoamine oxidase B) [249], VEGFC (vascular endothelial growth factor C) [250], DBP (D-box binding PAR bZIP transcription factor) [251], MYADM (myeloid associated differentiation marker) [252], NES (nestin) [253], SMURF1 [254], EDNRB (endothelin receptor type B) [255], MUC6 [256], TOR2A [257], TNKS (tankyrase) [258], NEDD9 [259], ASIC1 [260], ADAMTS8 [261], DYSF (dysferlin) [262], SLC26A9 [263], SLC45A3 [264] and KCNQ2 [265] contributes to the progression of hypertension, but these genes might be novel target for T1DM. Yang et al [266], Zhang et al [267] and Wang et al [268] demonstrated that SYVN1, BTG1 and CFB (complement factor B) were associated with diabetic retinopathy, but these genes might be novel target for T1DM.…”