CASIN and AMD3100 enhance endothelial cell proliferation, tube formation and sprouting

Kalkan, Batuhan Mert; Akgöl, Sezer; Ak, Deniz; Yücel, Doğacan; Esken, Gulen Guney; Kocabaş, Fatih

doi:10.1016/j.mvr.2020.104001

Cited by 9 publications

(5 citation statements)

References 72 publications

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“…Each compound was purchased at least at 1‐mg amounts and prepared the 10‐mM main stocks by dissolving in DMSO, as we have done previously (Aksoz et al, 2018; Kalkan et al, 2020). Small‐molecule main stocks were kept −20°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…On the fifth day, cells were stained with Hoechst 33342 (10 μg/ml) and Pyronin Y (100 μg/ml) after treatment with trypsin (0.25%). Samples were analyzed by flow cytometry (Beckman, Cytoflex S) as we have done previously (Aksoz et al, 2019; Kalkan et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…There is a large panel of small molecules that are used in cell expansion technologies (Aksoz et al, 2018; Kalkan et al, 2020; Yucel & Kocabas, 2018). Small molecules are molecules of low molecular weight (less than 500 Da).…”

Section: Introductionmentioning

confidence: 99%

“…This property allows them to enter cells and selectively act on signaling pathways (Gooderham, 2013; Torres & Filipe, 2015). Although small molecules have been identified for pancreatic 𝛽 cells (Shen et al, 2013), hematopoietic stem cells (Aksoz et al, 2018; Yucel & Kocabas, 2018), endothelial cells (Kalkan et al, 2020), or retinal pigment epithelial cell expansion (Swoboda et al, 2013), small‐molecule‐mediated expansion of dermal fibroblasts has not been thoroughly studied.…”

Section: Introductionmentioning

confidence: 99%

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Development of small‐molecule‐induced fibroblast expansion technologies

Sidal

Erkan

Uslu

et al. 2020

J Tissue Eng Regen Med

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Dermal fibroblasts are responsible from the production of extracellular matrix and take role in the closure of skin wounds. Dermal fibroblasts are major cells of origin in the generation of induced pluripotent stem cells (IPSCs) and are historically being used as feeder layer and biofiller in the restorative surgeries. ex vivo expansion of the dermal fibroblasts provides a suitable model to study skin biology and to engineer bioartifical skins. Thus, development of efficient fibroblast expansion technologies gets outmost importance day by day. We sought to identify small molecules that induce ex vivo fibroblast expansion and understand their mechanisms. We analyzed the effect of 35 small molecules, which are expected to target molecular pathways involving cellular quiescence. We have found that small molecules, especially AS1949490 and SKF96365, increase human dermal fibroblast expansion of at least three different fibroblasts. Cell cycle analysis confirms that these small molecules allow cell cycle progression, as evident by increased percentage of cells in S-G 2-M phase of cell cycle. They led to a lower profile of apoptotic or necrotic fibroblasts. Intriguingly, we have found that identified small molecules could also endogenously induce the expression of IPSC generation, collagen synthesis, and aging-related genes. Identified small molecules may contribute to the induction of collagen synthesis in the biofiller products, the development of fibroblast products with better aging profile, and the improvement of IPSC generation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of small‐molecule‐induced fibroblast expansion technologies

Sidal

Erkan

Uslu

et al. 2020

J Tissue Eng Regen Med

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“…The pCDNA3.1 vectors containing the recombinant OTU proteins were transfected into HEK293 cells with polyethyleneimine (PEI) (8)(9)(10)(11)(12). The day before transfection, 400,000 HEK293 cells were seeded into a 6-well plate.…”

Section: Transfection Of Malarial Otu-pcdna31 Mammalian Expression Vectorsmentioning

confidence: 99%

Identification of first-in-class plasmodium OTU inhibitors with potent anti-malarial activity

Siyah

Akgöl

Durdağı

et al. 2021

Biochemical Journal

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OTU proteases antagonize the cellular defense in the host cells and involve in pathogenesis. Intriguingly, P. falciparum, P. vivax, and P. yoelii have an uncharacterized and highly conserved viral OTU-like proteins. However, their structure, function or inhibitors have not been previously reported. To this end, we have performed structural modeling, small molecule screening, deconjugation assays to characterize and develop first-in-class inhibitors of P. falciparum, P. vivax, and P. yoelii OTU-like proteins. These Plasmodium OTU-like proteins have highly conserved residues in the catalytic and inhibition pockets similar to viral OTU proteins. Plasmodium OTU proteins demonstrated Ubiquitin and ISG15 deconjugation activities as evident by intracellular ubiquitinated protein content analyzed by western blot and flow cytometry. We screened a library of small molecules to determine plasmodium OTU inhibitors with potent anti-malarial activity. Enrichment and correlation studies identified structurally similar molecules. We have identified two small molecules that inhibit P. falciparum, P. vivax, and P. yoelii OTU proteins (IC50 values as low as 30nM) with potent anti-malarial activity (IC50 of 4.1-6.5 μM). We also established enzyme kinetics, druglikeness, ADME, and QSAR model. MD simulations allowed us to resolve how inhibitors interacted with plasmodium OTU proteins. These findings suggest that targeting malarial OTU-like proteases is a plausible strategy to develop new anti-malarial therapies.

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Identification of Small Molecules That Enhance the Expansion of Mesenchymal Stem Cells Originating from Bone Marrow

Alyazici

Kocabaş

2021

Advances in Experimental Medicine and Biology

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CASIN and AMD3100 enhance endothelial cell proliferation, tube formation and sprouting

Cited by 9 publications

References 72 publications

Development of small‐molecule‐induced fibroblast expansion technologies

Development of small‐molecule‐induced fibroblast expansion technologies

Identification of first-in-class plasmodium OTU inhibitors with potent anti-malarial activity

Identification of Small Molecules That Enhance the Expansion of Mesenchymal Stem Cells Originating from Bone Marrow

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