JNK and cardiometabolic dysfunction

Craige, Siobhan M.; Chen, Kai; Blanton, Robert M.; Keaney, John F.; Kant, Shashi

doi:10.1042/bsr20190267

Cited by 33 publications

(33 citation statements)

References 126 publications

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“…Mitogen‐activated protein kinase 8 (MAPK8), also known as JNK1, belongs to JNK kinase family that consists of three members: JNK1, JNK2 and JNK3 . JNK directly binds and promotes phosphorylation of several transcription factors, such as NFAT, c‐Jun and JunB, and regulates multiple biological processes, including immune cell differentiation, inflammation, cancer progression and especially programmed cell death . JNK can trigger apoptosis, promote necroptosis, involve in non‐canonical pyroptotic signalling and induce autophagy by different molecular mechanisms .…”

Section: Discussionmentioning

confidence: 99%

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Wang

Zhao

Xiao

et al. 2020

J Cellular Molecular Medi

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Glioblastoma multiforme (GBM) is a devastating brain tumour without effective treatment. Recent studies have shown that autophagy is a promising therapeutic strategy for GBM. Therefore, it is necessary to identify novel biomarkers associated with autophagy in GBM. In this study, we downloaded autophagy-related genes from Human Autophagy Database (HADb) and Gene Set Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to identify genes for constructing a risk signature. A nomogram was developed by integrating the risk signature with clinicopathological factors. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were used to evaluate the efficiency of the prognostic model. Finally, four autophagy-related genes (DIRAS3, LGALS8, MAPK8 and STAM)were identified and were used for constructing a risk signature, which proved to be an independent risk factor for GBM patients. Furthermore, a nomogram was developed based on the risk signature and clinicopathological factors (IDH1 status, age and history of radiotherapy or chemotherapy). ROC curve and calibration plot suggested the nomogram could accurately predict 1-, 3-and 5-year survival rate of GBM patients.For function analysis, the risk signature was associated with apoptosis, necrosis, immunity, inflammation response and MAPK signalling pathway. In conclusion, the risk signature with 4 autophagy-related genes could serve as an independent prognostic factor for GBM patients. Moreover, we developed a nomogram based on the risk signature and clinical traits which was validated to perform better for predicting 1-, 3-and 5-year survival rate of GBM. K E Y W O R D Sautophagy, glioblastoma multiform, nomogram, prognosis, risk signature

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Section: Discussionmentioning

confidence: 99%

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Wang

Zhao

Xiao

et al. 2020

J Cellular Molecular Medi

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“…Vascular diseases are related to changes in JNK expression 22 . Hui 51 showed that JNK plays a role in arteriosclerotic lesions.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of cell signalling pathways is one of the most important mechanisms for understanding how tissues respond to different events that alter cellular homeostasis [21]. Numerous studies have demonstrated the importance of the c-Jun N-terminal kinase (JNK) pathway in these processes, as it responds to and regulates the pathophysiological changes that occur [22]. The importance of JNK dysregulation lies in the impact it has on gene expression, cell viability and the extracellular matrix, affecting the effectiveness of the tissues of the involved organ [23][24][25].…”

Section: Ivyspringmentioning

confidence: 99%

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process

Ortega¹,

Asúnsolo²,

Pekarek³

et al. 2021

Int. J. Med. Sci.

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Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.

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“…It is well known that the MAPK signalling pathway also plays an important role in the pathogenesis of hypertension-induced cardiac remodelling and heart failure [ 7 , 34 , 35 ]. MAP kinases, predominantly p38 MAPK and JNK, are other important regulators of myocardial fibrosis [ 24 , 36 , 37 ]. The activity of MAP kinases are regulated by dual-specificity phosphatases (DUSPs) or MAPK phosphatases (MKPs) that can dephosphorylate MAPKs and in this way regulate—actually inhibit—their activity [ 34 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

BGP‐15 Protects against Heart Failure by Enhanced Mitochondrial Biogenesis and Decreased Fibrotic Remodelling in Spontaneously Hypertensive Rats

Horváth

Ördög

Bruszt

et al. 2021

Oxidative Medicine and Cellular Longevity

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Heart failure (HF) is a complex clinical syndrome with poor clinical outcomes despite the growing number of therapeutic approaches. It is characterized by interstitial fibrosis, cardiomyocyte hypertrophy, activation of various intracellular signalling pathways, and damage of the mitochondrial network. Mitochondria are responsible for supplying the energy demand of cardiomyocytes; therefore, the damage of the mitochondrial network causes cellular dysfunction and finally leads to cell death. BGP-15, a hydroxylamine derivative, is an insulin-sensitizer molecule and has a wide range of cytoprotective effects in animal as well as in human studies. Our recent work was aimed at examining the effects of BGP-15 in a chronic hypertension-induced heart failure model. 15-month-old male SHRs were used in our experiment. The SHR-Baseline group represented the starting point ( n = 7 ). Animals received BGP-15 (SHR-B, n = 7 ) or placebo (SHR-C, n = 7 ) for 18 weeks. WKY rats were used as age-matched normotensive controls ( n = 7 ). The heart function was monitored by echocardiography. Histological preparations were made from cardiac tissue. The levels of signalling proteins were determined by Western blot. At the end of the study, systolic and diastolic cardiac function was preserved in the BGP-treated animals. BGP-15 decreased the interstitial collagen deposition via decreasing the activity of TGFβ/Smad signalling factors and prevented the cardiomyocyte hypertrophy in hypertensive animals. BGP-15 enhanced the prosurvival signalling pathways (Akt/Gsk3β). The treatment increased the activity of MKP1 and decreased the activity of p38 and JNK signalling routes. The mitochondrial mass of cardiomyocytes was also increased in BGP-15-treated SHR animals due to the activation of mitochondrial biogenesis. The mitigation of remodelling processes and the preserved systolic cardiac function in hypertension-induced heart failure can be a result—at least partly—of the enhanced mitochondrial biogenesis caused by BGP-15.

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JNK and cardiometabolic dysfunction

Cited by 33 publications

References 126 publications

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process

BGP‐15 Protects against Heart Failure by Enhanced Mitochondrial Biogenesis and Decreased Fibrotic Remodelling in Spontaneously Hypertensive Rats

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