Science of the Month - May 2016
J Allergy Clin Immunol
2016 Feb 29; pii: S0091-6749(16)00111-1
Hiroshi Fujishima, Naoko Okada, Kenji Matsumoto, Kazumi Fukagawa, Ayako Igarashi, Akio Matsuda, Junya Ono, Shoichiro Ohta, Hideki Mukai, Mamoru Yoshikawa, and Kenji Izuhara
The diagnosis of ocular allergic diseases can sometimes be difficult. One possible reason is the lack of reliable biomarkers for a definitive diagnosis. In recent years, it has been suggested that the local "microenvironment" is important in the exacerbation of allergies. One of the important proteins that constitute this microenvironment is the extracellular matrix. It has been found that these transmit signals into cells that regulate cell proliferation, differentiation, and inflammation, and their role as cell function regulators has been gaining attention. These are called "matricellular proteins" and have been shown to be involved in various pathological conditions. Periostin is a matricellular protein belonging to the Fasciclin family. It has been previously shown that blood periostin levels are elevated in various allergic inflammatory diseases and diseases involving fibrosis. In this study, we focused on the tear fluid of patients with allergic conjunctivitis. As a result, we found that periostin was present at high concentrations in tear fluid and showed a more marked change than IL-13. Furthermore, it was revealed to be highly correlated with the symptoms of allergic conjunctivitis and the severity of the disease. This indicates that measuring periostin concentration in non-invasively collected tear fluid is highly useful as a new biomarker for the diagnosis and treatment of allergic conjunctivitis.
(Hiroshi Fujishima, Professor, Department of Ophthalmology, Tsurumi University School of Dental Medicine, Class of 1989)
2: Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells.
Cell Metabolism
Shugo Tohyama, Jun Fujita, Takako Hishiki, Tomomi Matsuura, Fumiyuki Hattori, Rei Ohno, Hideaki Kanazawa, Tomohisa Seki, Kazuaki Nakajima, Yoshikazu Kishino, Marina Okada, Akinori Hirano, Takuya Kuroda, Satoshi Yasuda, Yoji Sato, Shinsuke Yuasa, Motoaki Sano, Makoto Suematsu, Keiichi Fukuda
Human pluripotent stem cells (hPSCs), such as ES cells and iPS cells, are an attractive cell source for regenerative medicine, but a major problem is the contamination with undifferentiated stem cells that can cause tumors after differentiation. Therefore, we have focused on the role of metabolism in the survival of hPSCs. In this study, we revealed that glutamine plays an important role in coordination with glucose for the survival of hPSCs. When hPSCs were cultured under conditions where both glucose and glutamine were removed, ATP levels decreased markedly in a short time, and the cells died quickly, compared to when only glucose was removed. Furthermore, metabolome analysis revealed that hPSCs efficiently utilize glutamine, not pyruvate, to synthesize ATP. A possible reason for this is that the expression of aconitase 2 (ACO2) and isocitrate dehydrogenase 2/3 (IDH2/3) is remarkably low in hPSCs, while the expression of ATP citrate lyase (ACLY) is high (see figure). In contrast, cardiomyocytes were able to survive under the same conditions with the addition of lactate. The results of this research make it possible to produce clinical-grade cardiomyocytes with complete removal of undifferentiated stem cells inexpensively and easily, without using methods like FACS (cell sorters), and are expected to contribute to the realization of future regenerative medicine.
(Shugo Tohyama, Department of Cardiology, Class of 2000)