scholarly journals AMP-Activated Protein Kinase Regulates Intraocular Pressure, Extracellular Matrix, and Cytoskeleton in Trabecular Meshwork

2014 ◽  
Vol 55 (5) ◽  
pp. 3127 ◽  
Author(s):  
Ayan Chatterjee ◽  
Guadalupe Villarreal ◽  
Dong-Jin Oh ◽  
Min Hyung Kang ◽  
Douglas J. Rhee
Keyword(s):  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Protein Kinase ◽  
Trabecular Meshwork ◽  
Amp Activated Protein Kinase

scholarly journals SNHG3 cooperates with ELAVL2 to modulate cell apoptosis and extracellular matrix accumulation by stabilizing SNAI2 in human trabecular meshwork cells under oxidative stress

2020 ◽  
Author(s):  
Sizhen Li ◽  
Qingsong Yang ◽  
Zixiu Zhou ◽  
Min Fu ◽  
Xiaodong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Oxidative Damage ◽  
Trabecular Meshwork ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcellular Fractionation ◽  
Cell Counting

Abstract Background: Glaucoma is the main reason for irreversible blindness, and pathological increased intraocular pressure is the leading risk factor for glaucoma. It is reported that trabecular meshwork cell injury is closely associated with the elevated intraocular pressure. The current study aimed to investigate the role of SNHG3 in human trabecular meshwork (HTM) cells under oxidative stress. Methods: A series of experiments including real-time quantitative polymerase chain reaction (RT-qPCR), subcellular fractionation assay, western blot analysis, cell counting kit-8 (CCK-8) assay, RNA pull down, flow cytometry analysis, and RIP assay were employed to explore the biological function and regulatory mechanism of SNHG3 in HTM cells under oxidative stress.Results: First, we observed that H2O2 induced SNHG3 upregulation in HTM cells. Then, we found that SNHG3 silencing alleviated H2O2-induced oxidative damage in HTM cells. Moreover, SNAI2 knockdown alleviated the oxidative damage induced by H2O2 in HTM cells. Mechanistically, SNHG3 bound with ELAVL2 to stabilize SNAI2. Finally, SNAI2 overexpression counteracted the effect of SNHG3 silencing on H2O2-induced HTM cells. Conclusion: Our results demonstrated that SNHG3 cooperated with ELAVL2 to modulate cell apoptosis and extracellular matrix (ECM) accumulation by stabilizing SNAI2 in HTM cells under oxidative stress.

scholarly journals Fluctuations in Intraocular Pressure Increase the Trabecular Meshwork Extracellular Matrix

2014 ◽  
Vol 33 (4) ◽  
pp. 1215-1224 ◽  
Author(s):  
Huan Zou ◽  
Rongdi Yuan ◽  
Qijun Zheng ◽  
Yan Huo ◽  
Min Lang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Pressure Increase

scholarly journals Overexpression of SPARC in Human Trabecular Meshwork Increases Intraocular Pressure and Alters Extracellular Matrix

2013 ◽  
Vol 54 (5) ◽  
pp. 3309 ◽  
Author(s):  
Dong-Jin Oh ◽  
Min Hyung Kang ◽  
Yen Hoong Ooi ◽  
Kyu Ryong Choi ◽  
E. Helene Sage ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Trabecular Meshwork

scholarly journals AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

2015 ◽  
Vol 35 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Xia Luo ◽  
Lingyan Deng ◽  
Laxmi Pangeni Lamsal ◽  
Wenjuan Xu ◽  
Cheng Xiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
High Glucose ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Mtor Signaling Pathway ◽  
Matrix Synthesis ◽  
Matrix Accumulation ◽  
Amp Activated Protein Kinase

Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK) has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f). Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1) whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1). In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

scholarly journals Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

2004 ◽  
Vol 279 (19) ◽  
pp. 19502-19511 ◽  
Author(s):  
Jonathan B. Fitzgerald ◽  
Moonsoo Jin ◽  
Delphine Dean ◽  
David J. Wood ◽  
Ming H. Zheng ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Intracellular Calcium ◽  
Protein Kinase A ◽  
Expression Patterns ◽  
Cartilage Explants ◽  
Mechanical Forces ◽  
Amp Activated Protein Kinase ◽  
Kinase A

Chondrocytes are influenced by mechanical forces to remodel cartilage extracellular matrix. Previous studies have demonstrated the effects of mechanical forces on changes in biosynthesis and mRNA levels of particular extracellular matrix molecules, and have identified certain signaling pathways that may be involved. However, the broad extent and kinetics of mechano-regulation of gene transcription has not been studied in depth. We applied static compressive strains to bovine cartilage explants for periods between 1 and 24 h and measured the response of 28 genes using real time PCR. Compression time courses were also performed in the presence of an intracellular calcium chelator or an inhibitor of cyclic AMP-activated protein kinase A. Cluster analysis of the data revealed four main expression patterns: two groups containing either transiently up-regulated or duration-enhanced expression profiles could each be subdivided into genes that did or did not require intracellular calcium release and cyclic AMP-activated protein kinase A for their mechano-regulation. Transcription levels for aggrecan, type II collagen, and link protein were up-regulated ∼2–3-fold during the first 8 h of 50% compression and subsequently down-regulated to levels below that of free-swelling controls by 24 h. Transcription levels of matrix metalloproteinases-3, -9, and -13, aggrecanase-1, and the matrix protease regulator cyclooxygenase-2 increased with the duration of 50% compression 2–16-fold by 24 h. Thus, transcription of proteins involved in matrix remodeling and catabolism dominated over anabolic matrix proteins as the duration of static compression increased. Immediate early genes c-fosand c-junwere dramatically up-regulated 6–30-fold, respectively, during the first 8 h of 50% compression and remained up-regulated after 24 h.

scholarly journals Cathepsin K Regulates Intraocular Pressure by Modulating Extracellular Matrix Remodeling and Actin-Bundling in the Trabecular Meshwork Outflow Pathway

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2864
Author(s):  
Avinash Soundararajan ◽  
Sachin Anil Ghag ◽  
Sai Supriya Vuda ◽  
Ting Wang ◽  
Padmanabhan Paranji Pattabiraman
Keyword(s):  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Actin Cytoskeleton ◽  
Trabecular Meshwork ◽  
Critical Role ◽  
Constitutive Expression ◽  
Cathepsin K ◽  
Actin Dynamics ◽  
Actin Depolymerization ◽  
Outflow Pathway

The homeostasis of extracellular matrix (ECM) and actin dynamics in the trabecular meshwork (TM) outflow pathway plays a critical role in intraocular pressure (IOP) regulation. We studied the role of cathepsin K (CTSK), a lysosomal cysteine protease and a potent collagenase, on ECM modulation and actin cytoskeleton rearrangements in the TM outflow pathway and the regulation of IOP. Initially, we found that CTSK was negatively regulated by pathological stressors known to elevate IOP. Further, inactivating CTSK using balicatib, a pharmacological cell-permeable inhibitor of CTSK, resulted in IOP elevation due to increased levels and excessive deposition of ECM-like collagen-1A in the TM outflow pathway. The loss of CTSK activity resulted in actin-bundling via fascin and vinculin reorganization and by inhibiting actin depolymerization via phospho-cofilin. Contrarily, constitutive expression of CTSK decreased ECM and increased actin depolymerization by decreasing phospho-cofilin, negatively regulated the availability of active TGFβ2, and reduced the levels of alpha-smooth muscle actin (αSMA), indicating an antifibrotic action of CTSK. In conclusion, these observations, for the first time, demonstrate the significance of CTSK in IOP regulation by maintaining the ECM homeostasis and actin cytoskeleton-mediated contractile properties of the TM outflow pathway.

Sign in / Sign up

Export Citation Format

Share Document