Mechanical stretch upregulates connexin43 in human trabecular meshwork cells

Tellios, Nikoleta; Feng, Mary; Chen, Nancy; Liu, Hong; Tellios, Vasiliki; Wang, Mary; Li, Xiangji; Chang, Caitlin; Hutnik, Cindy

doi:10.1111/ceo.13492

Cited by 10 publications

(7 citation statements)

References 43 publications

(93 reference statements)

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“…In a model of intestinal damage, a previous study found that intestinal damage can be significantly relieved following administration of cx43 inhibitors (32). Another study demonstrated that stretch-induced apoptosis in human trabecular meshwork cells is accompanied by upregulation of Cx43 (33). The present findings indicated that Cx43 is involved in the apoptosis of Hcy-induced H9c2 cardiomyocytes.…”

Section: Discussionsupporting

confidence: 63%

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Chen

Ouyang

et al. 2020

Int J Mol Med

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Pirfenidone (PFd) is an anti-fibrotic agent that is clinically used in the treatment of idiopathic pulmonary fibrosis. PFd has been shown to exert protective effects against damage to orbital fibroblasts, endothelial cells, liver cells and renal proximal tubular cells; however, its effect on myocardial cell apoptosis remains unclear. The present study aimed to characterize the effects of PFd on homocysteine (Hcy)-induced cardiomyocyte apoptosis and investigated the underlying mechanisms. H9c2 rat cardiomyocytes were pre-treated with PFd for 30 min followed by Hcy exposure for 24 h. The effects of PFd on cell cytotoxicity were evaluated by ccK-8 assay. The apoptosis rate of each group was determined by flow cytometry. The protein and mRNA levels of connexin 43 (cx43), Bax, B-cell lymphoma-2 (Bcl-2) and caspase-3 were measured by western blot analysis and reverse transcription-quantitative PcR, respectively. The present results demonstrated that the apoptotic rate increased following Hcy exposure, whereas the apoptotic rate significantly decreased following PFd pre-treatment. Furthermore, the ratio of Bax/Bcl2 was upregulated following Hcy exposure, and Hcy upregulated the expression levels of cleaved caspase-3 and cx43. Notably, these effects were prevented by PFd. Additionally, the effects of PFd were inhibited by the Cx43 agonist, AAP10. In summary, the findings of the present study demonstrate that PFd protects H9c2 rat cardiomyocytes against Hcy-induced apoptosis by modulating the cx43 signaling pathway.

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Section: Discussionsupporting

confidence: 63%

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Chen

Ouyang

et al. 2020

Int J Mol Med

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“…The subunits, which include gap junctions, are the connexins which are integral membrane proteins. In order to form the gap junctions, one connexon hemichannel, formed by six connexins, has to bond to another connexon hemichannel present on an adjacent cell [ 230 , 231 ]. The mechanical stretch in HTMCs up-regulates connexin43 (Cx43) and its isoform.…”

Section: Trabecular Meshwork (Tm) and Location Of Outflow Resistanmentioning

confidence: 99%

“…The mechanical stretch in HTMCs up-regulates connexin43 (Cx43) and its isoform. However, recently, also Cx26 and/or Cx31 have been suggested as being involved in an increased intercellular signalling related to the altered TM [ 231 ].…”

Section: Trabecular Meshwork (Tm) and Location Of Outflow Resistanmentioning

confidence: 99%

Neuroinflammation in Primary Open-Angle Glaucoma

Vernazza

Tirendi

Bassi

et al. 2020

JCM

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Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

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“…From the Elisa assay, we concluded that there was an increased TGF beta1 protein concentration in cell culture medium under stretch stimulation. Taking into consideration that administration of TGF beta1 exogenously into some cells can stimulate Cx43 mRNA and protein expression, while in some different cells [11,12,15,16], ad-ministration of TGF beta1 can down-regulate Cx43 expression [17,18]. Therefore, it is importance to investigate whether administration of TGF beta1 can increase or decrease Cx43 mRNA or protein expression in HUVECs.…”

Section: Increased Tgfbeta1 Mrna and Protein Level After 24 H Stretchmentioning

confidence: 99%

Upregulation of Cx43 Expression Under Stretch Condition is Mediated by TGF Beta1 and Cytoskeletal Network

Shi¹,

Li²,

Yang³

2021

Preprint

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Many physiological and pathophysiological processes in cells or tissues are involving mechanical stretch, which is inducing gap junction gene expression and cytokine TGF beta changes. However, the underlying mechanisms of gap junction gene expression changes remain unknown. Here, we showed that the expression of Cx43 at mRNA and protein level in Human umbilical-vein endothelial cells (HUVECs) is significantly increased after 24 h stretch stimulation, and TGF beta1, but not TGF beta2 expression is also upregulated. Administration of TGF betal into HUVECs without stretch also induced upregulation of Cx43 mRNA and protein expression. While simultaneously administration of TGF beta1 with SB431542, a specific inhibitor of TGF beta1 receptor, blocked the Cx43 protein upregulation by TGF beta1. Further, the increase of Cx43 protein expression under stretch condition can be partially blocked by SB431542; moreover, it also can be partially blocked by simultaneously administration of anti-TGF beta1 monoclonal neutralization antibody. Importantly, the stretch induced upregulation of Cx43 can be blocked by administration of actin and microtubule inhibitors, while NEDD4, a key element in mediating Cx43 protein ubiquitination and degradation, is not changed under stretch condition. Therefore, we conclude that upregulation of Cx43 expression under 24 h stretch condition is mediated by TGF beta1 via TGF beta1 receptor signaling pathway, and it also involves the actin and microtubule cytoskeletal network.

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Mechanical stretch upregulates connexin43 in human trabecular meshwork cells

Cited by 10 publications

References 43 publications

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Neuroinflammation in Primary Open-Angle Glaucoma

Upregulation of Cx43 Expression Under Stretch Condition is Mediated by TGF Beta1 and Cytoskeletal Network

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