P21-activated kinase in inflammatory and cardiovascular disease

Taglieri, Domenico M.; Ushio‐Fukai, Masuko; Monasky, Michelle M.

doi:10.1016/j.cellsig.2014.04.020

Cited by 31 publications

(29 citation statements)

References 168 publications

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“…The downregulation of miR‐542‐5p has previously shown to be linked with advanced lymphatic metastasis, vascular invasion, TNM stage and EGFR, and survival analyses have widely highlighted that patients with lower miR‐542‐5p expression had poorer prognosis . P21‐activated kinases represent central regulators of the inflammatory response . PAK1 regulates the molecular mechanism of inflammation by the activation of its downstream target nicotinamide adenine dinucleotide phosphate oxidase in neutrophils .…”

Section: Discussionmentioning

confidence: 99%

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Wang

et al. 2018

J of Cellular Biochemistry

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Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

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Section: Discussionmentioning

confidence: 99%

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Wang

et al. 2018

J of Cellular Biochemistry

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“…Both Group I and II PAKs are important regulators of various biological processes including cell motility, survival, proliferation, and cytoskeletal organization. Owing to their involvement in the above physiological processes, deregulation of functional PAKs are implicated in multiple inflammatory disorders such as diabetes, cancer, mental retardation, allergy, inflammatory, and cardiovascular diseases ( 85 ).…”

Section: The New Rac1-p21-activated Kinase 1 (Pak1)-actin Remodeling mentioning

confidence: 99%

Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks: PAK-Ing Them Out

Tunduguru

Thurmond

2017

Front. Endocrinol.

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Glucose is the principal cellular energy source in humans and maintenance of glucose homeostasis is critical for survival. Glucose uptake into peripheral skeletal muscle and adipose tissues requires the trafficking of vesicles containing glucose transporter-4 (GLUT4) from the intracellular storage compartments to the cell surface. Trafficking of GLUT4 storage vesicles is initiated via the canonical insulin signaling cascade in skeletal muscle and fat cells, as well as via exercise-induced contraction in muscle cells. Recent studies have elucidated steps in the signaling cascades that involve remodeling of the cytoskeleton, a process that underpins the mechanical movement of GLUT4 vesicles. This review is focused upon an alternate phosphoinositide-3 kinase-dependent pathway involving Ras-related C3 botulinum toxin substrate 1 signaling through the p21-activated kinase p21-activated kinase 1 and showcases related signaling events that co-regulate both the depolymerization and re-polymerization of filamentous actin. These new insights provide an enriched understanding into the process of glucose transport and yield potential new targets for interventions aimed to improve insulin sensitivity and remediate insulin resistance, pre-diabetes, and the progression to type 2 diabetes.

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“…Previous studies have reported that PAK1 activation was responsible for initiation of inflammation [22]. Khare et al found that overexpression of PAK1 promoted cell survival in inflammatory bowel diseases and Western blot in human OA chondrocytes transfected with siRNA-NC or siRNA-PAK1, followed by treating with 10 ng/ml IL-1β for 24 h; n = 3, **P < 0.01.…”

Section: Discussionmentioning

confidence: 96%

Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction

Wang²,

Wang³

et al. 2020

Bioscience Reports

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Osteoarthritis is mainly caused by a degenerative joint disorder, which is characterized by the gradual degradation of articular cartilage and synovial inflammation. The chondrocyte, the unique resident cell type of articular cartilage, is crucial for the development of osteoarthritis. Previous studies revealed that P21-activated kinase-1 (PAK1) was responsible for the initiation of inflammation. The purpose of the present study was to determine the potential role of PAK1 in osteoarthritis. The level of PAK1 expression was measured by Western blot and quantitative real-time PCR in articular cartilage from osteoarthritis model rats and patients with osteoarthritis. In addition, the functional role of aberrant PAK1 expression was detected in the chondrocytes. We found that the expression of PAK1 was significantly increased in chondrocytes treated with osteoarthritis-related factors. Increased expression of PAK1 was also observed in knee articular cartilage samples from patients with osteoarthritis and osteoarthritis model rats. PAK1 was found to inhibit chondrocytes proliferation and to promote the production of inflammatory cytokines in cartilages chondrocytes. Furthermore, we found that PAK1 modulated the production of extracellular matrix and cartilage degrading enzymes in chondrocytes. Results of the present studies demonstrated that PAK1 might play an important role in the pathogenesis of osteoarthritis.

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P21-activated kinase in inflammatory and cardiovascular disease

Cited by 31 publications

References 168 publications

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks: PAK-Ing Them Out

Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction

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