Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway

Zu, Jianing; Wang, Yufu; Xu, Gongping; Zhuang, Jinpeng; He, Guoqing; Yan, Jun

doi:10.1016/j.acthis.2014.08.004

Cited by 58 publications

(44 citation statements)

References 37 publications

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“…In most of these studies conducted in both rats [80,81,82,83] and mice [84,85], SCI contusion and compression [64,86,87,88,89] induced a common pattern of AQP4 up-regulation. These preclinical trials have recently been reviewed in detail by Yonan and Binder [90].…”

Section: Aqp Expression In Disease Conditions Of Spinal Cordmentioning

confidence: 99%

Aquaporins in the Spinal Cord

Oklinski

Skowroński

Skowrońska

et al. 2016

IJMS

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Aquaporins (AQPs) are water channel proteins robustly expressed in the central nervous system (CNS). A number of previous studies described the cellular expression sites and investigated their major roles and function in the brain and spinal cord. Among thirteen different mammalian AQPs, AQP1 and AQP4 have been mainly studied in the CNS and evidence has been presented that they play important roles in the pathogenesis of CNS injury, edema and multiple diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, amyotrophic lateral sclerosis, glioblastoma multiforme, Alzheimer’s disease and Parkinson’s disease. The objective of this review is to highlight the current knowledge about AQPs in the spinal cord and their proposed roles in pathophysiology and pathogenesis related to spinal cord lesions and injury.

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Section: Aqp Expression In Disease Conditions Of Spinal Cordmentioning

confidence: 99%

Aquaporins in the Spinal Cord

Oklinski

Skowroński

Skowrońska

et al. 2016

IJMS

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“…Since JAK2 is highly expressed by cystic epithelial cells in vivo (Fig 1) we wondered whether its inhibition may be of therapeutic benefit and we set out to explore this biochemically in an in vitro setting. Studies in non-renal systems have suggested that curcumin, which is a natural phytochemical with strong anti-inflammatory activity and no appreciable side-effects, might be a JAK-STAT inhibitor 18-20 . We therefore studied the ability of curcumin to inhibit JAK/STAT in three independent ADPKD-derived epithelial cells, three lines were used to avoid cell line specific artefacts.…”

Section: Resultsmentioning

confidence: 99%

“…Studies in non-renal systems have suggested that curcumin might be a JAK-STAT inhibitor (15–17), however whether curcumin inhibits the JAK-STAT pathway in renal cells is unknown. To address this, human ADPKD-derived epithelial cells were treated with curcumin at 50μM for 6 hours, this concentration was used because it is the lowest dose that consistently caused a reduction in cystic growth (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

JAK2 is highly expressed by cyst-lining cells and regulates cystogenesis

Patera

Cudzuch-Mardy

Huang

et al. 2018

Preprint

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Autosomal dominant polycystic kidney disease (ADPKD) arises primarily due to Pkd1 mutations and is characterised by increased kidney epithelial proliferation. The Janus Kinase and Signal Transducers and Activators of Transcription (JAK-STAT) is a proliferation regulating pathway implicated in ADPKD. Curcumin, an anti-inflammatory phytochemical, has been shown to limit murine cystogenesis possibly via JAK-STAT. However, the mechanisms employed by curcumin to inhibit JAK-STAT are uncertain. We treated ADPKD-derived renal epithelial cells with curcumin at different concentrations over 9 days and studied their growth in organotypic cystforming assays. Curcumin potently blocked cystic growth in human and mouse renal epithelial cells without requiring any additional cell types, suggesting a direct effect on kidney epithelial cells. The level of tyrosine phosphorylated-STAT3 was reduced within 1 hour of curcumin treatment in a dose-dependent manner. While total STAT3 protein levels remained unaltered, suggesting that curcumin reduces phosphorylation of STAT3 possibly via JAK2, a tyrosine kinase upstream of STAT3. Mechanistically, curcumin caused JAK2 to move into an insoluble fraction, without causing JAK2 proteosomal-degradation. Instead curcumin led to JAK2 to accumulate into aggresomes, which are known depots for inactivated enzymes. We studied JAK2 expression in kidneys of the Pkd1 nl/nl mice, which spontaneously develop progressive ADPKD. JAK2 was highly expressed in cyst-lining renal epithelial cells at 5 and 10 weeks of age, suggesting a potential role in ADPKD pathophysiology. Collectively, these data suggest that curcumin reduces STAT3 signalling and cystic growth by inactivating JAK2, thus selective JAK2 inhibition may be of therapeutic benefit in ADPKD.

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“…Many pathological processes might be involved in spinal cord injury, such as edema, hypoxia, local ischemia, free radicals production and lipid peroxidation, and apoptosis [ 49 ]. A spinal cord injury-induced AQP4 overexpression has also been shown [ 37 ]. In a rat acute spinal cord injury model, Zu et al [ 37 ] evaluated the effect of curcumin on the motor function and spinal cord edema, showing that a single dose of curcumin administered via the intraperitoneal route at 30 min after acute spinal cord injury was able to moderately improve the motor dysfunction and tissue repair, to attenuate spinal cord edema, and to inhibit the overexpression of AQP4.…”

Section: Polyphenol Modulation Of Aquaporin Functionsmentioning

confidence: 99%

“…A spinal cord injury-induced AQP4 overexpression has also been shown [ 37 ]. In a rat acute spinal cord injury model, Zu et al [ 37 ] evaluated the effect of curcumin on the motor function and spinal cord edema, showing that a single dose of curcumin administered via the intraperitoneal route at 30 min after acute spinal cord injury was able to moderately improve the motor dysfunction and tissue repair, to attenuate spinal cord edema, and to inhibit the overexpression of AQP4. Authors also observed that during spinal cord injury the JAK/STAT signaling pathway was unusually activated, and further experiments showed that the curcumin protective effect was associated with the inhibition of this pathway.…”

Section: Polyphenol Modulation Of Aquaporin Functionsmentioning

confidence: 99%

Polyphenols as Modulators of Aquaporin Family in Health and Disease

Fiorentini

Zambonin

Sega

et al. 2015

Oxidative Medicine and Cellular Longevity

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Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP) isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

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Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway

Cited by 58 publications

References 37 publications

Aquaporins in the Spinal Cord

Aquaporins in the Spinal Cord

JAK2 is highly expressed by cyst-lining cells and regulates cystogenesis

Polyphenols as Modulators of Aquaporin Family in Health and Disease

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