Effects of TGFβ1, PDGF-BB, and bFGF, on human corneal fibroblasts proliferation and differentiation during stromal repair

Gallego‐Muñoz, Patricia; Ibares‐Frías, Lucía; Valsero-Blanco, M.Cruz; Cantalapiedra-Rodríguez, Roberto; Merayo‐Lloves, Jesús; Martínez‐García, Carmen

doi:10.1016/j.cyto.2017.03.011

Cited by 47 publications

(36 citation statements)

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“…However, the possibility that VEGF-A released by PRP may affect α-sma expression regardless of modulation of TGF-β1 signaling cannot be excluded. We can speculate that VEGF-A might exert its inhibitory action by cross-talking with other factors contained in PRP capable to act as antifibrotic agents, such as FGF-2 [ 64 , 86 , 87 , 88 ], or profibrotic ones such as PDGF [ 64 , 86 , 87 , 98 ], as reported in other cell types [ 99 , 100 ].…”

Section: Discussionmentioning

confidence: 97%

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

Chellini

Tani

Vallone

et al. 2018

Cells

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The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated inhibition of TGF-β1/Smad3 signaling. Indeed TGF-β1/PRP co-treated fibroblasts showed a robust attenuation of the myofibroblastic phenotype concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented the PRP-promoted effects. Moreover PRP abrogated the TGF-β1-induced reduction of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in counteracting myofibroblast generation was confirmed by cell treatment with soluble VEGF-A. PRP as single treatment did not induce fibroblast myodifferentiation. This study provides new insights into cellular and molecular mechanisms underpinning PRP antifibrotic action.

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Section: Discussionmentioning

confidence: 97%

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

Chellini

Tani

Vallone

et al. 2018

Cells

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“…Growth factors bFGF and PDGF-BB have been reported to be directly associated with corneal scarring by modulating fibroblast proliferation during wound healing. 46,47 Given that growth arrest is the typical characteristic of senescent cells, we measured the differences of mitogenic activity in response to bFGF or PDGF-BB among normal and senescent fibroblasts and myofibroblasts by CFSE labeling. In the process of cell division and proliferation, CFSE-labeled fluorescence intensity decreases step-by-step, as shown in Figures 4A and 4C; that is, the stronger fluorescence intensity represents less cell division.…”

Section: No Response Of Senescent Corneal Fibroblasts To Growth Factorsmentioning

confidence: 99%

Induction of Fibroblast Senescence During Mouse Corneal Wound Healing

Wang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Induction of fibroblast senescence during mouse corneal wound healing. Invest Ophthalmol Vis Sci. 2019;60:3669-3679. https://doi.org/10.1167/iovs.19-26983 PURPOSE. To investigate the presence and role of fibroblast senescence in the dynamic process of corneal wound healing involving stromal cell apoptosis, proliferation, and differentiation.METHODS. An in vivo corneal wound healing model was performed using epithelial debridement in C57BL/6 mice. The corneas were stained using TUNEL, Ki67, and a-smooth muscle actin (a-SMA) as markers of apoptosis, proliferation, and myofibroblastic differentiation, respectively. Cellular senescence was confirmed by senescence-associated bgalactosidase (SA-b-gal) staining and P16 Ink4a expression. Mitogenic response and gene expression were compared among normal fibroblasts, H 2 O 2 -induced senescent fibroblasts, and TGF-b-induced myofibroblasts in vitro. The senescence was further detected in mouse models of corneal scarring, alkali burn, and penetrating keratoplasty (PKP). RESULTS.The apoptosis and proliferation of corneal stromal cells were found to peak at 4 and 24 hours after epithelial debridement. Positive staining of SA-b-gal was observed clearly in the anterior stromal cells at 3 to 5 days. The senescent cells displayed P16 Ink4a þ vimentinþ a-SMAþ, representing the major origin of activated corneal resident fibroblasts. Compared with normal fibroblasts and TGF-b-induced myofibroblasts, H 2 O 2 -induced senescent fibroblasts showed a nonfibrogenic phenotype, including a reduced response to growth factor basic fibroblast growth factor (bFGF) or platelet-derived growth factor-BB (PDGF-BB), increased matrix metalloproteinase (MMP)1/3/13 expression, and decreased fibronectin and collagen I expression. Moreover, cellular senescence was commonly found in the mouse corneal scarring, alkali burn, and PKP models. CONCLUSIONS.Corneal epithelial debridement induced the senescence of corneal fibroblasts after apoptosis and proliferation. The senescent cells displayed a nonfibrogenic phenotype and may be involved in the self-limitation of corneal fibrosis.

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“…The difference in cytotoxicity of empty vector nanoplexes versus nanoplexes containing PDGFB pDNA could be explained by the proliferative effect of PDGF‐BB (Battegay, Rupp, Iruela‐Arispe, Sage, & Pech, ; Gallego‐Muñoz et al, ). In those samples that were transfected with nanoplexes containing PDGFB pDNA, the presence of PDGF‐BB may have been able to stimulate proliferation such that the viability loss upon exposure to the PEI from the nanoplexes was mostly recovered.…”

Section: Discussionmentioning

confidence: 99%

A proof of concept gene‐activated titanium surface for oral implantology applications

Laird

Malkawi

Chakka

et al. 2020

J Tissue Eng Regen Med

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Dental implants are very successful medical devices, yet implant failures do occur due to biological and mechanical complications. Peri-implantitis is one such biological complication that is primarily caused by bacteria and their products at the implant soft tissue interface. Bacterial infiltration can be prevented by the formation of a reliable soft tissue seal encircling dental implants. Platelet-derived growth factor-BB (PDGF-BB) has significant chemotactic and proliferative effects on various mesenchymal cell types, including fibroblasts, and therefore can be an effective molecule to enhance the peri-implant soft tissue seal. To overcome the limitations of the recombinant protein form of PDGF-BB, such as cost and the need for supraphysiological doses, we have developed and characterized a titanium surface that is rendered bioactive by coating it with polyethylenimine-plasmid DNA (pDNA) nanoplexes in the presence of sucrose. Human embryonic kidney 293T (HEK293T) cells and human primary gingival fibroblasts (GFs) were successfully transfected in culture with enhanced green fluorescent protein (EGFP)-encoding pDNA or platelet-derived growth factor subunit B (PDGFB)-encoding pDNA loaded into nanoplexes and coated onto titanium disks in a dose-dependent manner. GFs were shown to secrete PDGF-BB for at least 7 days after transfection and displayed both minimal viability loss and increased integrin-α2 expression 4 days posttransfection.

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Effects of TGFβ1, PDGF-BB, and bFGF, on human corneal fibroblasts proliferation and differentiation during stromal repair

Cited by 47 publications

References 50 publications

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †

Induction of Fibroblast Senescence During Mouse Corneal Wound Healing

A proof of concept gene‐activated titanium surface for oral implantology applications

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