Role of Adenosine Monophosphate-Activated Protein Kinase on Cell Migration, Matrix Contraction, and Matrix Metalloproteinase-1 and Matrix Metalloproteinase-2 Production in Nasal Polyp–Derived Fibroblasts

2017 ◽  
Vol 31 (6) ◽  
pp. 357-363 ◽  
Author(s):  
Ti-Young Um ◽  
Seoung-Ae Lee ◽  
Joo-Hoo Park ◽  
Jae-Min Shin ◽  
Il-Ho Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Nasal Polyp ◽  
Nasal Polyps ◽  
Tissue Remodeling ◽  
Adenosine Monophosphate ◽  
Compound C ◽  
Matrix Contraction

Purpose Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling. Here, we investigated the physical role of AMPK on cell migration, matrix contraction, and the production of matrix metalloproteinases (MMP) in nasal polyp–derived fibroblasts (NPDF). Methods Primary NPDFs from six patients with chronic rhinosinusitis and nasal polyps were isolated and cultured. To assess the effect of AMPK on fibroblast migration, we conducted scratch and migration assays in NPDF treated with metformin and/or compound C. A collagen gel contraction assay measured activity of contractile. MMP expression was measured with reverse transcription-polymerase chain reaction, Western blot, and zymography. To evaluate for specific AMPK action, we examined by AMPK small interfering RNA. Results Metformin, an activator of AMPK, significantly inhibited cell migration in NPDFs in a dose-dependent manner. Compound C, an inhibitor of AMPK, partially reversed the inhibitory effect of metformin. Metformin also significantly decreased contractile activity, with a concomitant reduction in the production of MMP-1 and MMP-2 but not of MMP-9. Specific silencing that targeted AMPK resulted in the enhancement of mobility and contractility and in the production of MMP-1 and MMP-2. Conclusion AMPK played an important role in regulating cell migration, matrix contraction, and MMP production in NPDFs, which provided data that AMPK activator might be a therapeutic target for the prevention of tissue remodeling in nasal polyps.

scholarly journals Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

2021 ◽  
Vol 22 (14) ◽  
pp. 7256
Author(s):  
Vianet Argelia Tello-Flores ◽  
Fredy Omar Beltrán-Anaya ◽  
Marco Antonio Ramírez-Vargas ◽  
Brenda Ely Esteban-Casales ◽  
Napoleón Navarro-Tito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Species ◽  
Necrosis Factor Alpha ◽  
Polypyrimidine Tract Binding Protein ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

scholarly journals The Role of CD68 (+) Histiocytic Macrophages in Nasal Polyp Development

2020 ◽  
Author(s):  
Nuray Bayar Muluk ◽  
Osman Kürşat Arikan ◽  
Pınar Atasoy ◽  
Rahmi Kiliç ◽  
Eda Tuna Yalçinozan
Keyword(s):  
Nasal Cavity ◽  
Nasal Polyp ◽  
Nasal Polyps ◽  
Deep Layer ◽  
Ethmoid Sinus ◽  
Adult Patients ◽  
Control Group ◽  
Study Group ◽  
Deep Layers

Abstract Objectives The aim of this study was to investigate the role of CD68 (+) histiocytic macrophages (H-M) in the nasal polyp pathogenesis. Materials and Methods The study group consisted of 24 adult patients with nasal polyposis. The control group consisted of 11 adult patients without nasal polyps. A total of 36 nasal polyp samples (10-nasal cavity, 10-maxillary sinus, and 16-ethmoid sinus) from the study group and 11 inferior turbinate samples from the control group were analyzed by immunohistochemical staining, with monoclonal antibodies against CD68 (+) H-M. Results CD68 positivity was significantly higher than the control group in the subepithelial (SE) layer of the ethmoid sinus, and deep layers of nasal cavity, maxillary, and ethmoid sinuses. In SE and deep layers of ethmoid and maxillary sinuses, CD68 positivity was significantly higher than that of the epithelial layer. In the deep layer, histiocytic macrophages tended to gather around eosinophils. Conclusion The high numbers of CD68 (+) histiocytic macrophages mainly located in deep layer of lamina propria may be responsible for the phagocytosis of eosinophils within the polyp tissue. Therefore, it may be concluded that increased macrophages in nasal polyps do not trigger the growth of nasal polyps. Instead, they may serve to reduce the number of eosinophils in already-developed nasal polyps.

scholarly journals Lipopolysaccharide-Induced Matrix Metalloproteinase-9 Expression Associated with Cell Migration in Rat Brain Astrocytes

2019 ◽  
Vol 21 (1) ◽  
pp. 259 ◽  
Author(s):  
Chien-Chung Yang ◽  
Chih-Chung Lin ◽  
Li-Der Hsiao ◽  
Jing-Ming Kuo ◽  
Hui-Ching Tseng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Rat Brain ◽  
P38 Map Kinase ◽  
Tanshinone Iia ◽  
Mitogen Activated Protein Kinase ◽  
Brain Diseases ◽  
Amino Terminal ◽  
Tyrosine Kinase 2

Neuroinflammation is a landmark of neuroinflammatory and neurodegenerative diseases. Matrix metalloproteinase (MMP)-9, one member of MMPs, has been shown to contribute to the pathology of these brain diseases. Several experimental models have demonstrated that lipopolysaccharide (LPS) exerts a pathological role through Toll-like receptors (TLRs) in neuroinflammation and neurodegeneration. However, the mechanisms underlying LPS-induced MMP-9 expression in rat brain astrocytes (RBA-1) are not completely understood. Here, we applied pharmacological inhibitors and siRNA transfection to assess the levels of MMP-9 protein, mRNA, and promoter activity, as well as protein kinase phosphorylation in RBA-1 cells triggered by LPS. We found that LPS-induced expression of pro-form MMP-9 and cell migration were mediated through TLR4, proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), platelet-derived growth factor receptor (PDGFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and Jun amino-terminal kinase (JNK)1/2 signaling molecules in RBA-1 cells. In addition, LPS-stimulated binding of c-Jun to the MMP-9 promoter was confirmed by chromatin immunoprecipitation (ChIP) assay, which was blocked by pretreatment with c-Src inhibitor II, PF431396, AG1296, LY294002, Akt inhibitor VIII, p38 MAP kinase inhibitor VIII, SP600125, and tanshinone IIA. These results suggest that in RBA-1 cells, LPS activates a TLR4/c-Src/Pyk2/PDGFR/PI3K/Akt/p38 MAPK and JNK1/2 pathway, which in turn triggers activator protein 1 (AP-1) activation and ultimately induces MMP-9 expression and cell migration.

scholarly journals Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts

2019 ◽  
Vol 316 (2) ◽  
pp. F253-F262 ◽  
Author(s):  
Josephine K. Liwang ◽  
Joseph A. Ruiz ◽  
Lauren M. LaRocque ◽  
Fitra Rianto ◽  
Fuying Ma ◽  
...  
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Adenosine Monophosphate ◽  
Osmotic Water Permeability ◽  
Water Reabsorption ◽  
Compound C ◽  
Ampk Phosphorylation ◽  
Osmotic Water ◽  
Medullary Collecting Duct

Hypertonicity increases water permeability, independently of vasopressin, in the inner medullary collecting duct (IMCD) by increasing aquaporin-2 (AQP2) membrane accumulation. We investigated whether protein kinase C (PKC) and adenosine monophosphate kinase (AMPK) are involved in hypertonicity-regulated water permeability. Increasing perfusate osmolality from 150 to 290 mosmol/kgH2O and bath osmolality from 290 to 430 mosmol/kgH2O significantly stimulated osmotic water permeability. The PKC inhibitors chelerythrine (10 µM) and rottlerin (50 µM) significantly reversed the increase in osmotic water permeability stimulated by hypertonicity in perfused rat terminal IMCDs. Chelerythrine significantly increased phosphorylation of AQP2 at S261 but not at S256. Previous studies show that AMPK is stimulated by osmotic stress. We tested AMPK phosphorylation under hypertonic conditions. Hypertonicity significantly increased AMPK phosphorylation in inner medullary tissues. Blockade of AMPK with Compound C decreased hypertonicity-stimulated water permeability but did not alter phosphorylation of AQP2 at S256 and S261. AICAR, an AMPK stimulator, caused a transient increase in osmotic water permeability and increased phosphorylation of AQP2 at S256. When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together. In conclusion, hypertonicity regulates water reabsorption by activating PKC. Hypertonicity-stimulated water reabsorption by PKC may be related to the decrease in endocytosis of AQP2. AMPK activation promotes water reabsorption, but the mechanism remains to be determined. PKC and AMPK do not appear to act synergistically to regulate water reabsorption.

scholarly journals Unexpected Role of Adenosine-Monophosphate Activated Protein Kinase in Doxorubicin Cardiotoxicity and Metformin-Mediated Cardioprotection

2019 ◽  
Vol 25 (8) ◽  
pp. S2
Author(s):  
Jaclyn Del Pozzo ◽  
Puja Mehta ◽  
Fei Cai ◽  
Cairong Li ◽  
Satoru Kobayashi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Adenosine Monophosphate ◽  
Doxorubicin Cardiotoxicity
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