Combined PI3K/Akt and Smad2 Activation Promotes Corneal Endothelial Cell Proliferation

Sabater, Alfonso L.; Andreu, Enrique J.; García-Guzmán, María; López, Tania; Abizanda, Gloria; Pérez, Víctor L.; Moreno-Montañés, Javier; Prósper, Felipe

doi:10.1167/iovs.16-20817

Cited by 24 publications

(14 citation statements)

References 27 publications

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“…It is also well known that IGF-1 promotes the proliferation of endothelial cells and perivascular smooth muscle cells via activation of the PI3K (phosphoinositide 3-kinase)/Akt pathway. 26,27 However, our immunohistochemical analyses did not reveal any differences in the fraction of proliferating Ki67 + cells within vehicle-, IGF-1-, and IGF-1/IGFbp4-exposed ad-MVFs. This is most probably due to the fact that the ad-MVFs were cultivated under hypothermic conditions, which have been shown to suppress cell proliferation.…”

Section: Discussionmentioning

confidence: 58%

Insulin-like growth factor 1 stimulates the angiogenic activity of adipose tissue–derived microvascular fragments

et al. 2019

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Angiogenesis in adipose tissue is promoted by insulin-like growth factor 1 signaling. We analyzed whether this regulatory mechanism also improves the angiogenic activity of adipose tissue–derived microvascular fragments. Murine adipose tissue–derived microvascular fragments were cultivated for 24 h in the University of Wisconsin (UW) solution supplemented with vehicle, insulin-like growth factor 1, or a combination of insulin-like growth factor 1 and insulin-like growth factor–binding protein 4. Subsequently, we assessed their cellular composition, viability, proliferation, and growth factor expression. Moreover, cultivated adipose tissue–derived microvascular fragments were seeded onto collagen–glycosaminoglycan scaffolds, which were implanted into dorsal skinfold chambers to study their vascularization and incorporation. Insulin-like growth factor 1 increased the viability and growth factor expression of adipose tissue–derived microvascular fragments without affecting their cellular composition and proliferation. Accordingly, scaffolds containing insulin-like growth factor 1–stimulated adipose tissue–derived microvascular fragments exhibited an enhanced in vivo vascularization and incorporation. These positive insulin-like growth factor 1 effects were reversed by additional exposure of adipose tissue–derived microvascular fragments to insulin-like growth factor–binding protein 4. Our findings indicate that insulin-like growth factor 1 stimulation of adipose tissue–derived microvascular fragments is suitable to improve their vascularization capacity.

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Section: Discussionmentioning

confidence: 58%

Insulin-like growth factor 1 stimulates the angiogenic activity of adipose tissue–derived microvascular fragments

et al. 2019

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“…To ascertain the potential role of AKT pathway on CT04-mediated inhibition of SC proliferation, we treated the SCs with CT04 in the presence or absence of AKT activators (IGF-1 (Jo et al, 2012 ; Sabater et al, 2017 ) or SC79 (Wu et al, 2017 ; Yang et al, 2018 ; Zhou et al, 2018 )), respectively. Western blotting indicated that IGF-1 dramatically increased the level of p-AKT while the level of total AKT was not affected (Figures 6A,B ).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Tan

Wen

et al. 2018

Front. Cell. Neurosci.

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Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway.

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“…It has been confirmed in rabbit models that the combined activation of PI3K/Akt and Smad2 leads to the expansion of phenotypic and functional corneal endothelial cells in vitro and expanded cells contribute to the recovery of corneal endothelium. 39 These findings may provide a new method for treating corneal endothelial diseases. The MAPK signaling pathway family is widely distributed in eukaryotic cells and has been associated with a variety of extracellular signals or stimuli, especially inflammatory responses.…”

Section: Significantly Enriched Pathways Associated With Fungal Keratmentioning

confidence: 88%

Transcriptome Analysis of the Gene Expression Profiles Associated with Fungal Keratitis in Mice Based on RNA-Seq

Zhang

Gong

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Fungal keratitis (FK) is an eye disease that can lead to blindness and has a high incidence worldwide. At present, there is no effective treatment for this disease. There are innate immune response mechanisms that protect against fungal infections. One example is C-type lectin receptors (CLRs), which can identify fungal invaders and trigger signal transduction pathways and cellular responses to eliminate pathogens. However, previous studies have focused mostly on single-receptor factors, and a systematic analysis of the genetic factors underlying the pathogenesis of FK has not been conducted. This study aimed to investigate the molecular mechanisms of FK in terms of genomics and to further elucidate its pathogenesis. METHODS. We performed a transcriptome analysis of a mouse model of FK using RNA sequencing to obtain the relevant gene expression profiles and to identify differentially expressed genes, signaling pathways, and regulatory networks of the key genetic factors in the pathogenesis of murine FK. RESULTS. Several genes that are significantly associated with FK and serve as markers of FK, such as the inflammatory cytokine genes IL1B, IL6, IL10, IL23, and TNF, were identified. The mRNA and protein expression patterns of IL-1β, IL-6, and TNF-α in the corneas of mice with FK were validated by quantitative RT-PCR and Luminex multiplex assay technology. The Wnt, cGMP-PKG, and Hippo signaling pathways were significantly enriched during fungal infection of mouse corneas. CONCLUSIONS. Our study may help to elucidate the mechanisms of FK pathogenesis and to identify additional candidate drug targets for the treatment of FK.

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Combined PI3K/Akt and Smad2 Activation Promotes Corneal Endothelial Cell Proliferation

Cited by 24 publications

References 27 publications

Insulin-like growth factor 1 stimulates the angiogenic activity of adipose tissue–derived microvascular fragments

Insulin-like growth factor 1 stimulates the angiogenic activity of adipose tissue–derived microvascular fragments

Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Transcriptome Analysis of the Gene Expression Profiles Associated with Fungal Keratitis in Mice Based on RNA-Seq

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