MiR-200c-3p regulates pyroptosis by targeting SLC30A7 in diabetic retinopathy

Clinical relevance: MicroRNAs (miRNAs) have been reported to be involved in the progression of various diseases. Studying the regulatory mechanisms of miRNAs can help clinical treatment. Background: Diabetic retinopathy (DR) is one of the complications of diabetes. The objective of this study was to elucidate the underlying molecular mechanisms by which miR-200c-3p regulates the pyroptosis of DR cell. Methods: Human retinal microvascular endothelial cells (HRMECs) and high glucose (HG) cultures established DR cell model in vitro. RT-qPCR is used to detect the expression level of miRNAs. CCK-8 assays and flow cytometry are used to detect apoptosis of HRMECs cell. Western blotting is used to detect cleaved caspase-3, cleaved caspase-1, and N-GSDMD proteins levels in HRMECs. The ELISA assay is used to detect the expression of IL-1β and IL-18. Predict and validate potential binding sites between miR-200c-3p and SLC30A7 by dual luciferase reporter gene analysis. Results: The results showed that HG caused damage to HRMECs through the pyroptosis pathway rather than the apoptosis pathway. MiR-200c-3p is highly expressed in HG induced-HRMECs, and knockdown of miR-200c-3p mitigates HG-induced HRMECs pyroptosis. MiR-200c-3p negatively targets SLC30A7 in HRMECs, and miR-200c-3p regulates pyroptosis of HG-induced HRMECs by targeting SLC30A7. Conclusion: The results suggest that miR-200c-3p might be a promising interference target for DR prevention and treatment. The results of current study may provide new insights into development of therapeutic strategies for DR.

[1]  Zhuge Xi,et al.  Ozone Exposure Promotes Pyroptosis in Rat Lungs via the TLR2/4-NF-κB-NLRP3 Signaling Pathway. , 2020, Toxicology.

[2]  H. Lv,et al.  DNMT1-mediated lncRNA MEG3 methylation accelerates endothelial-mesenchymal transition in diabetic retinopathy through the PI3K/AKT/mTOR signaling pathway. , 2020, American journal of physiology. Endocrinology and metabolism.

[3]  Qianqiu Wang,et al.  MiR‐223‐3p inhibits rTp17‐induced inflammasome activation and pyroptosis by targeting NLRP3 , 2020, Journal of cellular and molecular medicine.

[4]  Rui Yao,et al.  MiRNA-1 promotes pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1 through the FoxO3a pathway. , 2020, European review for medical and pharmacological sciences.

[5]  Mei Yang,et al.  miRNA‐200c‐3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts , 2020, The Journal of pathology.

[6]  Kai Zhang,et al.  MiRNA-214 promotes the pyroptosis and inhibits the proliferation of cervical cancer cells via regulating the expression of NLRP3. , 2020, Cellular and molecular biology.

[7]  S. Ylä-Herttuala,et al.  MicroRNA-15b Targets VEGF and Inhibits Angiogenesis in Proliferative Diabetic Retinopathy. , 2020, The Journal of clinical endocrinology and metabolism.

[8]  Hongming Shen,et al.  MicroRNA-148a-3p alleviates high glucose-induced diabetic retinopathy by targeting TGFB2 and FGF2 , 2020, Acta Diabetologica.

[9]  S. Srinivasan,et al.  Caspase-11-mediated enteric neuronal pyroptosis underlies Western diet-induced colonic dysmotility. , 2020, The Journal of clinical investigation.

[10]  K. Tsuchiya.  Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications , 2020, Microbiology and immunology.

[11]  Yuehua Jiang,et al.  MicroRNA-200c-3p inhibits proliferation and migration of renal artery endothelial cells by directly targeting ZEB2. , 2019, Experimental cell research.

[12]  Q. Mao,et al.  LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis , 2019, Stem Cell Research & Therapy.

[13]  X. Qin,et al.  Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy. , 2019, Experimental eye research.

[14]  P. Peplow,et al.  MicroRNAs as biomarkers of diabetic retinopathy and disease progression , 2019, Neural regeneration research.

[15]  Chufeng Gu,et al.  miR-590-3p Inhibits Pyroptosis in Diabetic Retinopathy by Targeting NLRP1 and Inactivating the NOX4 Signaling Pathway. , 2019, Investigative ophthalmology & visual science.

[16]  N. Delhomme,et al.  An AP2/ERF transcription factor ERF139 coordinates xylem cell expansion and secondary cell wall deposition. , 2019, The New phytologist.

[17]  Xiaowen Chi,et al.  Downregulation of microRNA-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating expression of RECK and inactivating the AKT signaling pathway. , 2019, Chemico-biological interactions.

[18]  Q. Dong,et al.  miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis , 2019, Oxidative medicine and cellular longevity.

[19]  P. Zhao,et al.  miR-200c-3p Suppresses the Proliferative, Migratory, and Invasive Capacities of Nephroblastoma Cells via Targeting FRS2. , 2019, Biopreservation and biobanking.

[20]  Z. Yao,et al.  miR-21 promotes NLRP3 inflammasome activation to mediate pyroptosis and endotoxic shock , 2019, Cell Death & Disease.

[21]  Jian-xing Ma,et al.  miRNA-451a regulates RPE function through promoting mitochondrial function in proliferative diabetic retinopathy. , 2019, American journal of physiology. Endocrinology and metabolism.

[22]  Xiaojia Wang,et al.  Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. , 2018, Oncology reports.

[23]  Yunlong Bai,et al.  Silencing long non-coding RNA Kcnq1ot1 alleviates pyroptosis and fibrosis in diabetic cardiomyopathy , 2018, Cell Death & Disease.

[24]  Xi Shen,et al.  Significant role of microRNA‑219‑5p in diabetic retinopathy and its mechanism of action. , 2018, Molecular medicine reports.

[25]  P. Fort,et al.  Role of Inflammation in Diabetic Retinopathy , 2018, International journal of molecular sciences.

[26]  Liping Huang,et al.  Aberrant fatty acid metabolism in skeletal muscle contributes to insulin resistance in zinc transporter 7 (znt7)-knockout mice , 2018, The Journal of Biological Chemistry.

[27]  G. Rutter,et al.  Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes. , 2018, Mitochondrion.

[28]  Shou-zhi He,et al.  miRNA-1273g-3p Involvement in Development of Diabetic Retinopathy by Modulating the Autophagy-Lysosome Pathway , 2017, Medical science monitor : international medical journal of experimental and clinical research.

[29]  Jieping Zhang,et al.  miR‐365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress , 2017, Experimental eye research.

[30]  L. Ding,et al.  Inhibition of translation initiation factor eIF4A is required for apoptosis mediated by Microplitis bicoloratus bracovirus. , 2017, Archives of insect biochemistry and physiology.

[31]  Jian-xing Ma,et al.  Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARα , 2017, Diabetes.

[32]  R. Benninger,et al.  Zinc Transport Gets Its Zing Back: Double-Knockout of ZnT7 and ZnT8 Reveals the Importance of Zinc Transporters to Insulin Secretion. , 2016, Endocrinology.

[33]  Tien Yin Wong,et al.  MICROVASCULAR COMPLICATIONS — RETINOPATHY ( JK SUN AND PS SILVA , 2016 .

[34]  J. K. Oeser,et al.  Combined Deletion of Slc30a7 and Slc30a8 Unmasks a Critical Role for ZnT8 in Glucose-Stimulated Insulin Secretion. , 2016, Endocrinology.

[35]  M. Mayr,et al.  Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes , 2015, Diabetes.

[36]  Liping Huang,et al.  Znt7-null Mice Are More Susceptible to Diet-induced Glucose Intolerance and Insulin Resistance* , 2012, The Journal of Biological Chemistry.

[37]  M. Ulbig,et al.  Diabetic retinopathy: Early diagnosis and effective treatment. , 2010, Deutsches Arzteblatt international.

[38]  J. Navarro,et al.  Inflammation and pathogenesis of diabetic nephropathy. , 2004, Metabolism: clinical and experimental.

[39]  A. Keech,et al.  Biomarkers in Diabetic Retinopathy. , 2015, The review of diabetic studies : RDS.