Oral Fibroblast Expression of wound-inducible transcript 3.0 (wit3.0) Accelerates the Collagen Gel Contraction in Vitro

Sukotjo, Cortino; Lin, A. T.; Song, Kevin; Ogawa, Takahiro; Wu, Bian; Nishimura, Ichiro

doi:10.1074/jbc.m309616200

Cited by 25 publications

(25 citation statements)

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“…Interestingly, clinical observations and experimental animal studies consistently indicate that wound healing in the oral mucosa has better outcomes than in the skin [16], [17], although the healing process and sequence are similar. Therefore, it has been postulated that oral mucosal cells possess distinctive characteristics promoting accelerated wound closure [18], [19]. The oral mucosa is composed of a thin keratinocyte layer with underlying connective tissue.…”

Section: Introductionmentioning

confidence: 99%

Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

et al. 2010

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BackgroundInduced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort.Methodology/Principal FindingsWe herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity.Conclusions/SignificanceThese results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection.

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Section: Introductionmentioning

confidence: 99%

Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

et al. 2010

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“…22 Once solidified at 37°C, fibroblast/gel was released from the well. The area of fibroblast/gel complex in digitized photographs was measured (Media Cybernetics, Bethesda, MD), and the ratio of collagen gel area against the culture well was calculated at each time point.…”

Section: Floating Collagen Gel Contraction Assaymentioning

confidence: 99%

“…The FGFR1OP2/wit3.0 allele is composed of seven exons and generates two isoforms of 215-amino acid (FGFR1OP2/wit3.0␣) and 253-amino acid (FGFR1OP2/wit3.0␤) through alternative splicing of exon 5. 22 The amino-terminal sequence of FGFR1OP2/wit3.0 encoded by the first four exons has been shown to facilitate the ligand-independent dimer formation of the FGFR1 tyrosin kinase domain in the cytogenetic abnormality (12;8) (p11; p11p22) ( Figure 1A), having caused acute myeloid leukemia. 23 FGFR1OP2/wit3.0 has been identified as a small cytoplasmic peptide expressed by oral wound fibroblasts 22 ; however, the function of native FGFR1OP2/wit3.0 has not been elucidated.…”

mentioning

confidence: 99%

“…22 The amino-terminal sequence of FGFR1OP2/wit3.0 encoded by the first four exons has been shown to facilitate the ligand-independent dimer formation of the FGFR1 tyrosin kinase domain in the cytogenetic abnormality (12;8) (p11; p11p22) ( Figure 1A), having caused acute myeloid leukemia. 23 FGFR1OP2/wit3.0 has been identified as a small cytoplasmic peptide expressed by oral wound fibroblasts 22 ; however, the function of native FGFR1OP2/wit3.0 has not been elucidated. We report here that FGFR1OP2/wit3.0 is a novel cytoskeleton molecule, with a regulatory role in fibroblast migration and rapid wound closure, a hallmark of oral wound healing.…”

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confidence: 99%

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Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

Lin

Hokugo

Choi

et al. 2010

The American Journal of Pathology

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Wounds created in the oral cavity heal rapidly and leave minimal scarring. We have examined a role of a previously isolated cDNA from oral wounds encoding wound inducible transcript-3.0 (wit3.0) , also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2). FGFR1OP2/wit3.0 was highly expressed in oral wound fibroblasts without noticeable up-regulation of ␣-smooth muscle actin. In silico analyses , denaturing and nondenaturing gel Western blot , and immunocytology together demonstrated that FGFR1OP2/wit3.0 were able to dimerize and oligomerize through coiled-coil structures and appeared to associate with cytoskeleton networks in oral wound fibroblasts. Overexpression of FGFR1OP2/ wit3.0 increased the floating collagen gel contraction of naïve oral fibroblasts to the level of oral wound fibroblasts , which was in turn attenuated by smallinterfering RNA knockdown. The FGFR1OP2/wit3.0 synthesis did not affect the expression of collagen I as well as procontractile peptides such as ␣-smooth muscle actin , and transforming growth factor-␤1 had no effect on FGFR1OP2/wit3.0 expression. Fibroblastic cells derived from embryonic stem cells carrying FGFR1OP2/wit3.0 (؉/؊) mutation showed significant retardation in cell migration. Thus , we postulate that FGFR1OP2/wit3.0 may regulate cell motility and stimulate wound closure. FGFR1OP2/wit3.0 was not upregulated during skin wound healing; however , when treated with FGFR1OP2/wit3.0 -expression vector, the skin wound closure was significantly accelerated, resulting in the limited granulation tissue formation. Our data suggest that FGFR1OP2/wit3.0 may possess a therapeutic potential for wound management. (Am J

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“…FGFR1OP2 is specifically induced in wound-associated oral fibroblasts, concomitant with an increase in the ability of these fibroblasts to contract collagen gel in vitro (Sukotjo et al, 2002). Increased FGFR1OP2 expression upon oral wounding is necessary and perhaps sufficient for the increased ability of wound fibroblasts to contract collagen gel in vitro (Lin et al, 2010, Sukotjo et al, 2002, Sukotjo et al, 2003). Moreover, FGFR1OP2 has also been reported to be important for fibroblast cell migration and to be induced to associate with the cytoskeleton upon oral wounding (Lin et al, 2010).…”

Section: Composition and Function Of Striatin Family Complexesmentioning

confidence: 99%

STRIPAK complexes: Structure, biological function, and involvement in human diseases

Hwang

Pallas

2014

The International Journal of Biochemistry & Cell Biology

207

273

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The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK–like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK or STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we will explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation.

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Oral Fibroblast Expression of wound-inducible transcript 3.0 (wit3.0) Accelerates the Collagen Gel Contraction in Vitro

Cited by 25 publications

References 31 publications

Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

STRIPAK complexes: Structure, biological function, and involvement in human diseases

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