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Department of Pathology

Overview

In this Department, we concentrate not only on education and research, which are two major missions in University, but also on pathological services including autopsy and diagnosis. Our main theme for research is the molecular mechanism in various diseases such as renal fibrosis, vascular calcification, and cancer. We are interested in renal interstitial fibrosis caused by ureteral obstruction in genetically engineered mice called Trps1 KO mice, expression pattern of clock genes, oncogenesis of myxoid liposarcoma, and tumor invasion and metastasis. While we usually use the animal model of a disease, we do research using biopsy samples and materials from autopsy as well. All staff member have an individual research theme, supervising graduate students. Graduate students obtain a PhD degree within four years. We focus on the translational research that has a direct connection to clinical issues, accepting some graduate students from other clinical Department. Autopsy, one of our pathological services, has been decreasing year by year; however, we can learn a lot of important information on a disease status from each case. For this reason, we try to share these information with as many students and doctors as possible through clinical-pathological conference (CPC). 

Education

We have classes and pathology lab to the 3rd grade of medical students. Also, we have classes for basic general pathology to the 1st grade students in School of Nursing. For graduate students, they do research under our supervision in the PhD course of four years to publish at least one paper written in English. Graduate students can choose to become a pathology specialist by learning how to make a microscopic diagnosis.

Introduction of staff

Yasuteru Muragaki Professor Molecular mechanisms of connective tissue diseases, Gene mutations of genetic disorders, Vascular calcification, Renal fibrosis
Yusuke Oikawa Lecturer Molecular mechanism of tumorigenesis
Fuyuki Sato Lecturer Expression patterns of clock genes
Masako Nakanishi Assistant Professor Mechanism of cancer bone metastasis, Molecular mechanism of cancer bone pain
Mayumi Akira General manager Production of pathological specimen
Haruhiko Sakamoto Part-time Lecturer Professor Emeritus of Kagawa Univesity
Takashi Ozaki Part-time Lecturer Development of thyroid, Microwave
Yoshihiro Ikura Part-time Lecturer Liver Pathology

Research

We have several research projects. First of all, we have been working on molecular mechanisms of hereditary osteochondral dysplasia. We are focusing on TRPS, which is an autosomal dominant disorder characterized by sparse hair, cone-shaped epiphysis, pear-like nose, and facial skeletal abnormalities. We have identified a mutation in a family with the disease. To investigate the function of TRPS1 protein, we produced KO mice that are deficient in the Trps1 protein. Using the Trps1 KO mice, we have discovered that Trps1 regulates the proliferation and apoptosis of growth plate chondrocytes. Also, we have demonstrated that Trps1 is expressed in proximal tubular epithelial cells and essential to nephron formation. Furthermore, we have shown that Trps1 inhibits renal interstitial fibrosis by suppressing TGF-b signaling via a decreased activity of Smad3. In addition, we have been examining the expression of clock genes, such as DEC1, DEC, and Bmal1 in a variety of tissues. Other research projects we focus on in this lab are the molecular mechanisms of tumorigenesis of myxoid chondrosarcoma, invasion and metastasis to lymph nodes of breast cancer, and vascular calcification.  

In addition to the basic research, we have been working on clinical pathology research using pathology specimens to investigate gene expression in several kinds of cancer cells.

Publications

Trps1 functions downstream of Bmp7 in kidney development. Gai Z, Zhou G, Itoh S, Morimoto Y, Tanishima H, Hatamura I, Uetani K, Ito M, Muragaki Y. J Am Soc Nephrol. 20(11):2403-11, 2009
Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats. Okada T, Sakaguchi T, Hatamura I, Saji F, Negi S, Otani H, Muragaki Y, Kawachi H, Shigematsu T. Clin Exp Nephrol. 13(5):438-46, 2009
Occurrence of central polydactyly, syndactyly, and cleft hand in a single family: report of five hands in three cases. Satake H, Ogino T, Takahara M, Kikuchi N, Muramatsu I, Muragaki Y, Kano H. 
J Hand Surg Am.34(9):1700-3, 2009
SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. Nishioka R, Itoh S, Gui T, Gai Z, Oikawa K, Kawai M, Tani M, Yamaue H, and Muragaki Y. Exp. Mol. Pathol 89: 149-157, 2010
Trps1 haploinsufficiency promotes renal fibrosis by increasing Arkadia expression. Gai Z, Zhou G, Gui T., Itoh S, Oikawa K, Uetani K, and Muragaki Y. J. Am. Soc. Nephrol 21: 1468-1476, 2010
The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles. Gai Z, Gui T, Muragaki Y. Histol Histopathol. 26(7):915-21, 2011
Prolyl hydroxylase in human corpora lutea during menstrual cycle and early pregnancy. Iwahashi M, Muragaki Y. Fertil Steril. 95(1):345-8, 2011
Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing. Kawakatsu M, Kanno S, Gui T, Gai Z, Itoh S, Tanishima H, Oikawa K, Muragaki Y.
Exp Mol Pathol. 90(1):107-15, 2011
Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice. Kanno S, Gui T, Itoh S, Gai Z, Sun Y, Oikawa K, Yoshida M, Muragaki Y.
Exp Mol Pathol. 90(2):143-8, 2011
Increased type I and V collagen expression in uterine leiomyomas during the menstrual cycle. Iwahashi M, Muragaki Y. Fertil Steril. 95(6):2137-9, 2011
The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles. Gai Z, Gui T, Muragaki Y. Histol Histopathol. 26(7):915-21. Review, 2011
Prolyl hydroxylase in human corpora lutea during menstrual cycle and early pregnancy. Iwahashi M, Muragaki Y. Fertil Steril. 95(1):345-8, 2011                            Snail is a useful biomarker for the diagnosis of gastric carcinoma in biopsy samples.   Tanishima H, Gui T, Sun Y, Shimokado A,Ozaki T,Muragaki Y. ISRN Pathology 2012, 132472, 2012
Fibulin-5 Protein Is Reduced in the Lung of Patients with Spontaneous Pneumothorax Who Are Under 25 Years Old. Hirai Y, Muragaki Y, Itoh S, Oikawa K, Juri M, Kondo T, Okamura Y. Ann Thorac Cardiovasc Surg. 18(3):200-5, 2012
The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-β-Induced Epithelial-Mesenchymal Transition. Gui T, Sun Y, Shimokado A, Muragaki Y.              J Signal Transduct. 2012:289243, 2012
Diverse roles of macrophages in atherosclerosis: from inflammatory biology to biomarker discovery. Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y. Mediators Inflamm. 2012: 693083, 2012
A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression. Oikawa K, Tanaka M, Itoh S, Takanashi M, Ozaki T, Muragaki Y, Kuroda M. Br J Cancer. 106(12):1976-9, 2012
MicroRNAs that target Ca2+ transporters are involved in vascular smooth muscle cell calcification. Gui T, Zhou G, Sun Y, Shimokado A, Itoh S, Oikawa K, Muragaki Y.
Lab Invest. 92: 1250–1259, 2012
The loss of Trps1 suppresses ureteric bud branching because of the activation of TGF-b signaling. Gui T, Sun Y, Gai Z, Shimokado A, Muragaki Y, Zhou G.
Dev Biol. 15;377(2):415-27, 2013
Uterine damage in swine following uterine artery embolization: comparison among gelatin sponge particles and two concentrations of N-butyl cyanoacrylate. Sonomura T, Kawai N, Ikoma A, Minamiguchi H, Ozaki T, Kishi K, Sanda H, Nakata K, Nakai M, Muragaki Y, Sato M. Jpn J Radiol. 2013 Oct;31(10):685-92, 2013
The role of Tricho-Rhino-Phalangeal Syndorome (TRPS) 1 in apoptosis during embryonic development and tumor progression. Sun Y, Gui T, Shimokado A, Muragaki Y. Cells 2(3): 496-505, 2013
Elevated serum 1,25(OH)2-vitamin D3 level attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in kl/kl mice. Sun Y, Zhou G, Gui T, Shimokado A, Nakanishi M, Oikawa K, Sato F, Muragaki Y. Sci Rep 4: 6563, 2014
Smad3 plays an inhibitory role in phosphate-induced vascular smooth muscle cell calcification. Shimokado A, Sun Y, Nakanishi M, Sato F, Oikawa K, Akasaka T, Muragaki Y. Exp Mol Pathol 97: 458-464, 2014
Cell culture of human gingiva fibroblasts, oral cancer cells and mesothelioma cells with serum-free media, STK1 and STK2. Tsugeno Y, Sato F, Muragaki Y, and Kato Y. Biomed Rep. 2(5): 644-648, 2014
The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice. Kohsaka A, Das P, Hashimoto I, Nakao T, Deguchi Y, Gouraud S S, Waki H, Muragaki Y, Maeda M. Plos One 12;9(11):e112811, 2014
Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression. Sun Y, Nakanishi M, Sato F, Oikawa K, Muragaki Y, Zhou G. Biochem Biophys Res Commun. 456(3):721-6, 2015
B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia. Hanaoka N, Murata S, Hosoi H, Shimokado A, Mushino T, Kuriyama K, Hatanaka K, Nishikawa A, Kurimoto M, Sonoki H, Muragaki Y, Nakakuma H. Hematol Rep, 7:5906: 56-59, 2015
DEC1 and DEC2 crosstalk between circadian rhythm and tumor progression. Sato F, Bhawal UK, Yoshimura T, Muragaki Y. J Cancer  7(2):153-9, 2016
DEC1 negatively regulates AMPK activity via LKB1. Sato F, Muragaki Y, Zhang Y. Biochem Biophys Res Commun. ;467(4):711-6, 2015