Vitamin D<sub>3</sub> Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway

Antony

Medicinal Research Reviews

et al. 2020

The innate immune system contains multiple classes of pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the intracellular and extracellular space. Although PRRs are indispensable for the detection and clearance of invading pathogens, dysregulated PRR activation by extrinsic and intrinsic factors leads to inflammatory diseases. PRRmediated inflammation has been shown to play a pivotal role in the pathogenesis of diabetic vascular complications (DVCs), which are the leading causes of morbidity and mortality in diabetic patients. Upon sensing hyperglycemiagenerated DAMPs, PRRs activate intracellular signaling pathways leading to the production of proinflammatory cytokines and chemokines in various cells of the kidney, brain, eye, and heart. The resulting chronic, low-grade inflammation contributes to DVCs. In this review, we summarize the role of PRRs in DVCs including diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. We propose that targeting PRRs and associated signaling pathways may be beneficial for the management of DVCs.

Section: Nlrs In Drmentioning

confidence: 99%

Pattern recognition receptor‐mediated inflammation in diabetic vascular complications

Antony

Medicinal Research Reviews

et al. 2020

“…However, the target relation between miR‐20b‐3p and TXNIP has not been uncovered yet. Furthermore, inflammasomes act as an intracellular machinery to initiate inflammatory response to many danger signals, and the relation between TXNIP and nucleotide‐binding oligomerization domain‐like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes in DR has been unveiled by several literatures …”

Section: Introductionmentioning

confidence: 99%

Elevated microRNA‐20b‐3p and reduced thioredoxin‐interacting protein ameliorate diabetic retinopathy progression by suppressing the NLRP3 inflammasomes

et al. 2020

IUBMB Life

Over the years, microRNA‐20b‐3p (miR‐20b‐3p) has been found to play an essential role in human diseases; we aimed to investigate the effect of miR‐20b‐3p on the progression of diabetic retinopathy (DR). The DR rat models were established by streptozotocin injection and treated with miR‐20b‐3p mimics, silenced, or overexpressed thioredoxin‐interacting protein (TXNIP). Afterward, the expression of miR‐20b‐3p and TXNIP, visual function, inflammatory factors, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in rats' retinal tissues were assessed. The target relation between miR‐20b‐3p and TXNIP was confirmed by dual luciferase reporter gene assay. MiR‐20b‐3p was poorly expressed while TXNIP was highly expressed in DR rats' retinal tissues. Elevated miR‐20b‐3p and inhibited TXNIP promoted the visual function, and restricted the inflammatory reaction, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in DR rats, thereby decelerating the development of DR. Furthermore, TXNIP was targeted by miR‐20b‐3p. We have found in this study that elevated miR‐20b‐3p could repress the levels of inflammatory factors by inhibiting TXNIP, thus attenuating the pathology of retina in DR rats, which provided new candidates for DR treatment.

“…The TXNIP/NLRP3 in ammasome plays a key role in the pathogenesis of various diseases [30,32,34,35]. Chen W et al [9] have indicated that minocycline improves diabetic retinopathy by inhibiting the TXNIP/NLRP3 in ammasome pathway, and Vitamin D3 attenuates diabetic retinopathy by inhibiting high-glucose-induced ROS/TXNIP/NLRP3 in ammasome pathway [36]. In the present study, we found that the TXNIP/NLRP3 in ammasome components were upregulated in EAE mice, and bixin remarkably downregulated the expression of TXNIP and NLRP3 at both mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 99%

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 inflammasome Activity and Activating Nrf2 Signaling

et al. 2020

Preprint

Background Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation.Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammation, and anti-tumor. However, the effects of bixin on MS remain elusive.Methods To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated with intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay analyses were performed.Results We found that bixin significantly improved the symptoms in EAE mice, and suppressed microglia aggregation and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS). Furthermore, bixin activated nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes in EAE mice, and these effects were suppressed upon inhibiting Nrf2 expression with the Nrf2 inhibitor ML385.Conclusions Bixin prevented neuroinflammation and demyelination in EAE mice mainly by scavenging ROS through activation of the Nrf2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate to treat MS.