Cyclosporine A Induces Nerve Growth Factor Expression Via Activation of MAPK p38 and NFAT5

Lee, Joon H; Kim, Jee Won; Im, Young Sun; Seong, Gong Je

doi:10.1097/ico.0b013e3182281028

Cited by 17 publications

(20 citation statements)

References 30 publications

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“…Notably, TonEBP increases the enzyme activity of AR, which is itself associated with abnormalities in osmotic and oxidative stress factors that promote diabetic complications, including neurodegeneration. Furthermore, TonEBP participates in the upregulation of tumor necrosis factor family genes and NF-κB activation [37] . Because NF-κB features predominantly in various neurodegenerative diseases and regulates proinflammatory enzyme expression [16,17] , our current results suggest that TonEBP may stimulate the NF-κB pathway as a downstream signaling target, leading to neurodegeneration in the diabetic retina.…”

Section: Discussionmentioning

confidence: 99%

Aralia elata Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

Kim

Yoo

Kim³

et al. 2015

Ophthalmic Res

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Background/Aims: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. Methods: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. Results: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. Conclusions: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.

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Section: Discussionmentioning

confidence: 99%

Aralia elata Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

Kim

Yoo

Kim³

et al. 2015

Ophthalmic Res

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“…There is also evidence in SCI rats that NGF (both mRNA and protein levels) are increased in bladder (261). NGF, which is elevated in patients with DO (187), mediates a number of processes (via activation of multiple signal transduction pathways), including epithelial signaling, cell growth, proliferation, and differentiation (9,177,260). In patients with NDO, there is a corresponding increase in NGF protein that is decreased or normalized with treatment with BoNT-A (115).…”

Section: Neurogenic Injurymentioning

confidence: 99%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

399

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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“…However, it remains unclear whether additional pathways, such as nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB), are important in this process. Notably, there is a Rel domain that preserves a DNA-binding sequence with homology to NF-κB in the regulatory region of NFATs (17). Further studies are required to explore their roles of enhancing the proliferation and differentiation of cartilage in OA.…”

Section: Discussionmentioning

confidence: 99%

Role of nuclear factor of activated T cells 1 in the pathogenesis of osteoarthritis

Sun

Zhang

Chen

et al. 2013

Experimental and Therapeutic Medicine

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Osteoarthritis (OA) is the most common form of joint disease in middle-aged individuals and the elderly. Previous studies have shown that the overexpression of matrix-degrading proteinases and proinflammatory cytokines is associated with the degradation of osteoarthritic cartilage. However, the transcription factors involved remain unclear. The present study aimed to determine the expression levels of nuclear factor of activated T cells 1 (NFAT1), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in patients with OA, and to validate the role of NFAT1 in the pathogenesis of OA. The expression levels of NFAT1, IL-1β and TNF-α in chondrocytes in the cartilage of patients with OA and healthy individuals were evaluated using western blot analysis. A luciferase reporter assay was performed to determine the activity of NFAT1 in primary human chondrocytes that were transfected with pNFAT1-luc plasmid and stimulated by IL-1β. An enzyme-linked immunosorbent assay was performed to detect the levels of TNF-α, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 in the supernatant of cultured chondrocytes in which the NFAT1 was silenced. The expression levels of NFAT1, IL-1β and TNF-α in the cartilage of patients with OA were higher than those of the controls. IL-1β induced the expression of NFAT1 in primary chondrocytes. The expression levels of TNF-α, MMP-1, -3 and -9 promoted by IL-1β were decreased in NFAT1-silenced chondrocytes. In conclusion, NFAT1 may be important in the pathogenesis of OA and calcineurin-NFAT inhibitors may be potential effective agents for the treatment of OA.

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Cyclosporine A Induces Nerve Growth Factor Expression Via Activation of MAPK p38 and NFAT5

Abstract: CsA is a potent inducer of NGF in the HCECL. These results suggest that CsA mediates NGF expression through activation of p38 and NFAT5.

Cited by 17 publications

References 30 publications

<b><i>Aralia elata</i></b> Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

<b><i>Aralia elata</i></b> Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

Urothelial Signaling

Role of nuclear factor of activated T cells 1 in the pathogenesis of osteoarthritis

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