Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats

“…It has reported that TUDCA could protect streptozotocin (STZ)-induced diabetic retinopathy rats [19]. In addition, a recent study has suggested that some chemical inhibitors of ER stress may be helpful in diabetic glomerulopathy [20].…”

Section: Introductionmentioning

confidence: 99%

Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

et al. 2016

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Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.

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“…The following may be responsible for this desirable effect: UDCA attenuated vascular destruction based on our findings and restored BRB breakdown by abrogating the NFκB-mediated inflammatory signaling pathway 20 , which inhibited the progression of retinal ischemia and therefore suppressed VEGF expression; UDCA suppressed macrophage-derived VEGF according to our result of immunostaining results. Moreover, in terms of the action mechanism of UDCA, a previous study showed that tauroursodeoxycholic acid (formed by the conjugation of UDCA with taurine) suppressed the increased expression of VEGF in high glucose-induced retinal microvascular endothelial cells 28 , demonstrating that UDCA also functions targeting the vascular endothelium.…”

Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models

Shiraya

Araki

Ueta

et al. 2020

Sci Rep

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As a clinical manifestations of diabetic retinopathy (DR), pericytes (pcs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in pc depletion mice by injection of an antibody against platelet-derived growth factor reception-β (pDGfR-β clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80 + macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR. Diabetes and its related complications, including retinopathy, have a great social and economic burden worldwide 1,2. The World Health Organization has suggested that diabetic retinopathy (DR) is responsible for 15-17% of total blindness cases in the United States and Europe 1,3-5. Pericytes (PC) not only provide mechanical support, but also maintain vessel wall integrity by interacting with endothelial cells (EC) via secretory signals and direct cell-to-cell contact 6. As an early clinical manifestation of DR, PC depletion from the capillary wall is considered an early pathological change that causes the blood-retinal barrier (BRB) to collapse and subsequent vascular hyperpermeability 7. Furthermore, PC depletion results in vascular abnormalities along with upregulation of angiogenic factors and inflammatory cytokines 8,9. In cases of more advanced DR, vascular occlusion induces retinal hypo-perfusion and hypoxia, resulting in abnormal angiogenesis that directly causes blindness due to vitreous hemorrhage and tractional retinal detachment 10. In recent years, intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents have been effectively used to treat diabetic macular edema 11-13 and have also empirically indicated the involvement of the VEGF signaling and inflammation in BRB breakdown in DR 14. However, frequent injections are burdensome for patients and physicians, and are associated with a very high cost to the healthcare system. Preventative medicine of DR with a safe and low-burden treatment for patients that requires investigation. Ursodeoxycholic acid (UDCA), a product of the hydrolysis of taurour...

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Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats

Cited by 51 publications

References 19 publications

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models

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Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats

Cited by 51 publications

References 19 publications

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-&alpha;-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-&alpha;-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models

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Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment