Publications by authors named "M Narimatsu"

56 Publications

A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone.

Bone Res 2020 Nov 23;8(1):41. Epub 2020 Nov 23.

Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) play important roles in bone metabolism. Smad ubiquitination regulatory factors (Smurfs) regulate TGF-β/BMP signaling via ubiquitination, resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling. Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling, its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated. In the present study, we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism. Absorbable collagen sponges containing 3 μg of recombinant human BMP2 (rhBMP2) were implanted in the dorsal muscle pouches of wild type (WT) and Smurf2 mice. The rhBMP2-induced ectopic bone in Smurf2 mice showed greater bone mass, higher mineral apposition and bone formation rates, and greater osteoblast numbers than the ectopic bone in WT mice. In WT mice, the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone. In contrast, in Smurf2 mice, the induced bone consisted of a thick, continuous outer cortical shell and abundant inner trabecular bone. Additionally, rhBMP2-stimulated bone marrow stromal cells (BMSCs) from Smurf2 mice showed increased osteogenic differentiation. Smurf2 induced the ubiquitination of Smad1/5. BMP/Smad signaling was enhanced in Smurf2 BMSCs stimulated with rhBMP2, and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs. These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling, thereby identifying a new regulatory mechanism in bone metabolism.
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http://dx.doi.org/10.1038/s41413-020-00115-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680794PMC
November 2020

Adapted Three-step Restorative Technique: Recovering Dental Substrate Compromised by Complex Erosive Wear in a Young Patient.

Oper Dent 2020 Sep;45(5):457b-466

Clinical Relevance: This article presents the dental restoration of a young female patient complaining of erosive dental wear using a three-step restorative technique, an alternative approach with some novel adjustments.

Summary: For successful tooth wear treatment, determining the etiological systemic and local factors is the main priority before deciding on effective and long-term preventive and/or therapeutic restorative approaches. In addition to professional intervention, achieving optimal outcomes requires patients to control their diet and/or gastric issues, thus minimizing the wear process. However, continuous wear constitutes the most challenging scenario, mainly when it affects young patients' dentitions. This article describes the dental restoration of posterior teeth with reestablishment of occlusal vertical dimension before treating the anterior teeth, while educating the patient and providing medical monitoring. The three-step restorative technique seems to be properly applicable in cases of significant dental compromise due mainly to erosive wear and is based on direct procedures, which can assure a reliable and feasible approach.
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http://dx.doi.org/10.2341/18-204-SDOI Listing
September 2020

Tricholoma matsutake may take more nitrogen in the organic form than other ectomycorrhizal fungi for its sporocarp development: the isotopic evidence.

Mycorrhiza 2019 Jan 8;29(1):51-59. Epub 2018 Nov 8.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.

Tricholoma matsutake is an ectomycorrhizal (ECM) fungus capable of in vitro saprotrophic growth, but the sources of C and N used to generate sporocarps in vivo are not well understood. We examined natural abundance isotope data to investigate this phenomenon. For this purpose, C, N and their stable isotopes (C, N) content of fungal sporocarps and their potential nutrient sources (i.e., foliage, litter, fine roots, wood, and soil) were investigated from two well-studied sites in Finland and Japan. Our results show that δC values of T. matsutake and other fungal groups are consistent with those of most studies, but a very high δN value (16.8‰ ± 2.3) is observed in T. matsutake. Such isotopic pattern of fungal δN suggests that matsutake has a greater proteolytic potential to digest chemically complex N-enriched organic matter and hydrophobic hyphae. This assumption is further supported by a significant and positive correlation between δC and δN exclusively in T. matsutake, which suggests common C and N sources (protein) possible for isotopically enriched cap. The C increase of caps relative to stipe presumably reflects greater contents of C-enriched protein than C-depleted chitin. We conclude that T. matsutake is a typical ECM fungus which obtains for its sporocarp development for both C and N from a common protein source (vs. photosynthetic carbon) present in soil organic matter.
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http://dx.doi.org/10.1007/s00572-018-0870-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311186PMC
January 2019

A feed forward loop enforces YAP/TAZ signaling during tumorigenesis.

Nat Commun 2018 08 29;9(1):3510. Epub 2018 Aug 29.

Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.

In most solid tumors, the Hippo pathway is inactivated through poorly understood mechanisms that result in the activation of the transcriptional regulators, YAP and TAZ. Here, we identify NUAK2 as a YAP/TAZ activator that directly inhibits LATS-mediated phosphorylation of YAP/TAZ and show that NUAK2 induction by YAP/TAZ and AP-1 is required for robust YAP/TAZ signaling. Pharmacological inhibition or loss of NUAK2 reduces the growth of cultured cancer cells and mammary tumors in mice. Moreover, in human patient samples, we show that NUAK2 expression is elevated in aggressive, high-grade bladder cancer and strongly correlates with a YAP/TAZ gene signature. These findings identify a positive feed forward loop in the Hippo pathway that establishes a key role for NUAK2 in enforcing the tumor-promoting activities of YAP/TAZ. Our results thus introduce a new opportunity for cancer therapeutics by delineating NUAK2 as a potential target for re-engaging the Hippo pathway.
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http://dx.doi.org/10.1038/s41467-018-05939-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115388PMC
August 2018

The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development.

Sci Rep 2018 06 22;8(1):9542. Epub 2018 Jun 22.

Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.

Smad ubiquitin regulatory factor 1 (SMURF1) is a HECT-type E3 ubiquitin ligase that plays a critical role in vertebrate development by regulating planar cell polarity (PCP) signaling and convergent extension (CE). Here we show that SMURF1 is involved in mammalian heart development. We find that SMURF1 is highly expressed in outflow tract cushion mesenchyme and Smurf1 mouse embryos show delayed outflow tract septation. SMURF1 is expressed in smooth muscle cells of the coronary arteries and great vessels. Thickness of the aortic smooth muscle cell layer is reduced in Smurf1 mouse embryos. We show that SMURF1 is a negative regulator of cardiomyogenesis and a positive regulator of smooth muscle cell and cardiac fibroblast differentiation, indicating that SMURF1 is important for cell-type specification during heart development. Finally, we provide evidence that SMURF1 localizes at the primary cilium where it may regulate bone morphogenetic protein (BMP) signaling, which controls the initial phase of cardiomyocyte differentiation. In summary, our results demonstrate that SMURF1 is a critical regulator of outflow tract septation and cell-type specification during heart development, and that these effects may in part be mediated via control of cilium-associated BMP signaling.
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http://dx.doi.org/10.1038/s41598-018-27854-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015040PMC
June 2018
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