Differential Effects of Transforming Growth Factor-β2 on Corneal Endothelial Cell Proliferation – A Role of Serum Factors

Chen, Ko Hua; Hsu, Wen Ming; Lee, Shui Mei

doi:10.1006/exer.2002.1180

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…The present results show the cell cycle to be accelerated from the G0/G1 to the S‐phase. These results are consistent with those of some (Plouët & Gospodarowicz 1989; Rieck et al 1995) but not all previous reports (Zieske et al 2001; Chen et al 2002). The discrepancy may be attributable to differences in experimental conditions.…”

Section: Discussionsupporting

confidence: 94%

“…We did, however, obtain valuable preliminary information regarding the cell cycle regulation of corneal endothelial cells in situ . There is a possible explanation for the divergent results in the effects of TGF‐β on the cell cycle of cultured endothelial cells (Plouët & Gospodarowicz 1989; Rieck et al 1995; Zieske et al 2001; Chen et al 2002). In many cell types, including epithelial cells, the switch from stimulation to inhibition of the cell cycle progression may be regulated by the balance between the inhibitors (TGF‐β in the present experiment) and the stimulators (PDGF‐BB in the present experiment).…”

Section: Discussionmentioning

confidence: 99%

“…TGF‐β has been reported to stimulate the migration, proliferation and extracellular matrix production of cultured corneal endothelial cells (Plouët & Gospodarowicz 1989; Usui et al 1998; Grant et al 1992; Rieck et al 1995). TGF‐β also reportedly inhibits the proliferation of corneal endothelial cells (Zieske et al 2001; Chen et al 2002). In many cell types, including epithelial, vascular endothelial and blood cells, TGF‐β inhibits cell proliferation by blocking cell cycle progression from the G0/G1 phase to the S‐phase.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of bovine corneal endothelial cell cycle by transforming growth factor‐β

Motegi¹,

Usui²,

Ishida³

et al. 2003

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: The transforming growth factor-b (TGF-b) family includes three multifunctional proteins, TGF-b1, TGF-b2 and TGF-b3, expressed in ocular tissue, which are involved in regulating cell differentiation, cell proliferation and other cell functions. TGF-b is present in aqueous humour and regulates corneal endothelial cells. This study explores the mechanism by which TGF-b regulates the cell cycle in cultured corneal endothelial cells. Methods: The expression of specific receptors for the TGF-b family was investigated at the protein level by affinity cross-linking with radio-iodinated TGF-b1 and immunoprecipitation with specific antibodies to TGF-b receptors. Regulation of entry into the S-phase of the cell cycle was determined by 5-bromo-2 0 deoxyuridine (BrdU) incorporation into the cells. The signal transduction pathways were investigated using various blocking agents for protein kinase transducers involved in intracytoplasmic signal transduction. Results: Cultured bovine corneal endothelial cells were confirmed to express TGF-b type 1 and type 2 receptors and endoglin. In the confluent state, TGFb1 and TGF-b2 stimulated the cells to progress to the S-phase of the cell cycle through platelet-derived growth factor-B (PDGF-B) chain production and protein kinase C. Conclusions: TGF-b accelerated cell cycle progression from the G0/G1 phase to the S-phase in cultured corneal endothelial cells, under our experimental conditions, through pathways involving protein kinase C. These pathways are related to the cross-talk between TGF-b and other cytokines. The conditions employed in the present experiments may be useful for investigating the complex cross-talk between various cytokines and growth factors.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of bovine corneal endothelial cell cycle by transforming growth factor‐β

Motegi¹,

Usui²,

Ishida³

et al. 2003

Acta Ophthalmologica Scandinavica

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“…It was present in our PRs only at 0.1∼0.5 ng/ml, a dose which might be sufficient to enhance CEC growth when combined with the other platelet growth factors. The role of TGF-β may be more ambiguous as it may at certain concentrations alter CEC expansion and induce formation of myofibroblasts and corneal scarring [38], [54] and lead to endothelial-mesenchymal transition [33]. Conversely, TGF-β exerts an anti-inflammatory role in ocular disorders and infections [15].…”

Section: Discussionmentioning

confidence: 99%

Ex vivo Expansion of Bovine Corneal Endothelial Cells in Xeno-Free Medium Supplemented with Platelet Releasate

2014

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Clinical-grade ex vivo expansion of corneal endothelial cells can increase the availability of corneal tissues for transplantation and treatment of corneal blindness. However, these cells have very limited proliferative capacity. Successful propagation has required so far to use very complex growth media supplemented with fetal bovine serum and other xenocomponents. We hypothesized that human platelet releasates rich in multiple growth factors, and in particular neurotrophins, could potentially be a useful supplement for ex vivo expansion of corneal endothelium cells due to their neural crest origin. Platelet releasates were prepared by calcium salt activation of apheresis platelet concentrates, subjected or not to complement inactivation by heat treatment at 56°C for 30 minutes. Platelet releasates were characterized for their content in proteins and were found to contain high amount of growth factors including platelet-derived growth factor-AB (30.56 to 39.08 ng/ml) and brain-derived neurotrophic factor (30.57 to 37.11 ng/ml) neurotrophins. We compared the growth and viability of corneal endothelium cells in DMEM-F12 medium supplemented with different combinations of components, including 2.5%∼10% of the platelet releasates. Corneal endothelium cells expanded in platelet releasates exhibited good adhesion and a typical hexagonal morphology. Their growth and viability were enhanced when using the complement-inactivated platelet releasate at a concentration of 10%. Immunostaining and Western blots showed that CECs maintained the expressions of four important membrane markers: Na-K ATPase α1, zona occludens-1, phospho-connexin 43 and N-cadherin. In conclusion, our study provides the first proof-of-concept that human platelet releasates can be used for ex vivo expansion of corneal endothelium cells. These findings open a new paradigm for ex vivo propagation protocols of corneal endothelium cells in compliance with good tissue culture practices and regulatory recommendations to limit the use of xenogenic materials.

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“…Moreover, serum-derived factors may change the microenvironment of the anterior chamber and the ocular cell response to cytokines in the aqueous humor. In vivo serum influx through a compromised blood-ocular barrier influences the responses of ocular cells to cytokines in the aqueous humor [ 18 , 19 ]. Therefore, we simultaneously compared serum and aqueous levels of TNF-α, IL-2, TGF-β2 and IL-4 and investigated the possible effects of cytokine levels on clinical characteristics and postoperative outcomes in glaucoma patients.…”

Section: Introductionmentioning

confidence: 99%

Aqueous humor cytokine levels are associated with the severity of visual field defects in patients with primary open-angle glaucoma

et al. 2023

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Background To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. Methods Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-β2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. Results TNF-α and TGF-β2 showed significantly higher AH levels in the POAG group than in the cataract group (P < 0.001 and P = 0.001, respectively). For the POAG group, preoperative IOPs were significantly positively correlated with AH levels of TNF-α (r2 = 0.129, P = 0.027) and TGF-β2 (r2 = 0.273, P = 0.001). AH levels of TGF-β2 were significantly different among cataract patients, POAG patients with MD> -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. Conclusion The levels of TNF-α and TGF-β2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-β2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.

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Differential Effects of Transforming Growth Factor-β2 on Corneal Endothelial Cell Proliferation – A Role of Serum Factors

Cited by 6 publications

References 32 publications

Regulation of bovine corneal endothelial cell cycle by transforming growth factor‐β

Regulation of bovine corneal endothelial cell cycle by transforming growth factor‐β

Ex vivo Expansion of Bovine Corneal Endothelial Cells in Xeno-Free Medium Supplemented with Platelet Releasate

Aqueous humor cytokine levels are associated with the severity of visual field defects in patients with primary open-angle glaucoma

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