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Matsuda Miho Last modified date:2018.05.08

Associate Professor / Division of Oral Biological Sciences
Department of Dental Science
Faculty of Dental Science


Graduate School


E-Mail
Homepage
http://www.dent.kyushu-u.ac.jp/sosiki/a04/index.html
Phone
092-642-6321
Fax
092-642-6322
Academic Degree
PhD
Field of Specialization
molecular biology biochemistry cell biology
Research
Research Interests
  • Function of a novel inositol 1,4,5-trisphosphate binding protein, PRIP, in the regulation of reproductive system
    keyword : hormone, secretion, reproductive system, gonadotropin
    2006.05.
  • Study on the function of PRIP in the regulation of bone metabolism
    keyword : bone metabolism, signal transduction, PRIP, hormone, secretion
    2008.04.
Current and Past Project
  • Study on the involvement of a novel signaling molecule, PRIP in the regulation of bone metabolism.
  • Study on Ca2+ dependent regulation of gene expressions.
  • Study on brain specific regulation of PRIP-1 gene expression.
Academic Activities
Papers
1. Matsuda, M, Tsutsumi, K., Kanematsu, T., Fukami, K., Terada, Y., Takenawa, T., Nakayama, K.I., Hirata, M., Involvement of phospholipase C-related inactive protein in the mouse reproductive system through the regulation of gonadotropin levels. , Biology of reproduction, 81, 681, 2009.07.
Presentations
1. Phospholipase C-related catalytically inactive protein (comprising PRIP-1 and -2) was first identified as a novel inositol 1,4,5-trisphosphate binding protein, but the biological functions have remained elusive. We therefore generated PRIP-1 and -2 double knockout (DKO) mice and found their reduced fertility: DKO mice exhibited reduced fertility in the female such as decreased number of pups, longer estrous days, increased secretion of gonadotropins, etc. This time we examined the ability of the ovaries in response to gonadotropins: the total number of the ovulated oocytes were remarkably decreased in DKO female mice, indicating that PRIP plays an important role in follicle maturation and/or ovulation, but not fertilization or implantation. Microarray and quantitative real-time PCR analyses revealed the increased expressions of molecules involved in ovulation including Has2, Ptgs2, PTX3, Tnfaip6 and Areg in both genotype. We examined the ability of COC expansion in both genotypes but little difference was observed. On the other hand, histological analysis revealed more immature follicles and fewer mature follicles or corpus lutea in DKO ovaries. Immunological analysis showed the expression of luteinizing hormone receptors (LHR) at earlier stages of follicle maturation in DKO ovary, and elevated level of ERK phosphorylation in DKO granulosa cells. These results suggest that the appearance of LHR at immature follicle stages leads to suppress follicle maturation by excessive LH signaling in DKO ovary, indicating that PRIP may be involved in positive regulation of ovarian follicle maturation through LH signaling. .
2. Phospholipase C-related catalytically inactive protein (comprising PRIP-1 and -2) was first identified as a novel inositol 1,4,5-trisphosphate binding protein, but the biological functions have remained elusive. We therefore generated PRIP-1 and –2 double knockout (DKO) mice to gain insight into the biological function. DKO mice exhibited reduced fertility in the female such as decreased number of pups, longer estrous days, increased secretion of gonadotropins, etc. We examined the ability of the ovaries in response to gonadotropins: the total number of the ovulated oocytes were remarkably decreased in DKO female mice, indicating that PRIP plays an important role in follicle maturation and/or ovulation, but not fertilization or implantation. Microarray and quantitative real-time PCR analyses revealed the increased expressions of molecules involved in ovulation including Has2, Ptgs2, PTX3, Tnfaip6 and Areg. We examined the ability of COC expansion in both genotypes but little difference was observed. On the other hand, histological analysis of ovaries from both genotypes revealed more immature follicles and fewer mature follicles or corpus lutea in DKO ovaries. Immunofluorescence analysis showed the expression of luteinizing hormone receptors (LHR) at earlier stages of follicle maturation in DKO ovary and more increase of antral follicles. These results are summarized as below: the increased LH secretion from pituitary gland and the appearance of LHR at immature follicle stages lead excessive LH signaling to suppress follicle maturation in DKO females, indicating that PRIP may be involved in positive regulation of ovarian follicle maturation through LH signaling. .
3. Miho Matsuda, Masato Hirata, Involvement of a novel signaling molecule, PRIP in the regulation of reproduction system
, The 22th IUBMB, 37st FEBS Congress, 2012.09.06.
4. Phospholipase C-related but catalytically inactive protein (comprising PRIP-1 and -2) was first identified as a novel D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] binding protein, but the biological functions have remained elusive. We therefore generated PRIP-1 and –2 double knockout (DKO) mice to gain insight into the biological function. DKO mice showed dysfunction of the reproductive system in the female. We examined the ability of the ovaries in response to gonadotropins: the total number of the ovulated oocytes were significantly decreased in mutant female mice, compared to that seen with wild-type, which was also confirmed by histological analysis of the ovaries after ovulation. These results suggested that PRIP plays an important role in not fertilization or implantation but follicle maturation and/or ovulation. Microarray analysis indicated the increased expressions of ovulation related molecules such as Has2, Ptgs2, PTX3, Tnfαip6 and Ereg. Historogical analysis of ovaries, just before ovulation, showed some abnormal follicles in the DKO. We also examined the ability of COC expansion in both genotypes and the significantly difference was not observed. On the other hand, TUNEL assay was performed to detect apoptotic follicles related to follicle maturation. There were some differences between in WT and DKO ovaries, depending on the follicle stages. Further analyses are underway to reveal the role of PRIP on follicle maturation and ovulation. .
5. Phospholipase C-related but catalytically inactive protein (comprising PRIP-1 and -2) was first identified as a novel D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] binding protein, but the biological functions have remained elusive. We therefore generated PRIP-1 and –2 double knockout (DKO) mice to gain insight into the biological function. DKO mice apparently grew normally and became fertile; however, during animal maintenance, we noticed that mutant couples exhibited decreased litter events and litter size, indicating dysfunction of the reproductive system. Cross-mating experiments indicated that the cause appeared to be on the female side. The observation of the estrous cycle in mice by histological analysis of vaginal smears showed that the estrous days were apparently increased in DKO mice. Levels of serum LH and FSH were measured for 5-6 consecutive days, and were significantly higher in the mutant, which was also confirmed by examining the secretion of LH from the explant culture of anterior pituitary glands of wild-type and DKO mice. We also examined the ability of the ovaries in response to gonadotropins: the total number of the ovulated oocytes were significantly decreased in mutant female mice, compared to that seen with wild-type, which was also confirmed by histological analysis of the ovaries after ovulation. These results suggest that PRIP plays an important role in female reproductive system, especially in gonadotropin secretion, ovarian follicle maturation and ovulation..
6. Phospholipase C-related but catalytically inactive protein (comprising PRIP-1 and -2) was first identified as a novel D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] binding protein, but the biological functions have remained elusive. We therefore generated PRIP-1 and –2 double knockout (DKO) mice to gain insight into the biological function. DKO mice apparently grew normally and became fertile; however, during animal maintenance, we noticed that mutant couples exhibited decreased litter events and litter size, indicating dysfunction of the reproductive system. Cross-mating experiments indicated that the cause appeared to be on the female side. The observation of the estrous cycle in mice by histological analysis of vaginal smears showed that the estrous days were apparently increased in DKO mice. Levels of serum LH and FSH were measured for 5-6 consecutive days, and were significantly higher in the mutant, which was also confirmed by examining the secretion of LH from the explant culture of anterior pituitary glands of wild-type and DKO mice. We also examined the ability of the ovaries in response to gonadotropins: the total number of the ovulated oocytes were significantly decreased in mutant female mice, compared to that seen with wild-type, which was also confirmed by histological analysis of the ovaries after ovulation. The analysis also showed that the numbers of follicles originally were not significantly different between WT and DKO ovaries. These results suggest that PRIP plays an important role in female reproductive system, especially in gonadotropin secretion and ovarian follicle maturation..
7. PRIP (phospholipase C related, but catalytically inactive protein) was identified as a novel inositol 1,4,5-trisphosphate binding protein, whose domain organization is similar to that of phospholipase C-_1 but is catalytically inactive, comprizing two isoforms, PRIP-1 and PRIP-2. To get insight into the biological functions, we generated the double knockout (DKO) mice of both PRIP-1 and PRIPミ2, followed by the phenotypic analyses. DKO mice grew normally and became fertile. However DKO female exhibited the decreased litter occasion and litter size, indicating the dysfunction of female reproductive system. Then we examined the estrus cycle by cytological analysis of daily vaginal smears, resulting in the irregular cycle in DKO mice. We further noticed that the mutant mice had apparently smaller sized uterus by gross anatomical observation. Basal levels of serum leuteinizing hormone and follicle stimulating hormone were significantly higher in the mutant, the event of which was also confirmed by examining the secretion from the tissue culture of anterior pituitary glands. These results suggest that PRIP is involved in maternal reproduction, through the gonadotropine secretion..
8. PRIP (phospholipase C related, but catalytically inactive protein) was identified as a novel inositol 1,4,5-trisphosphate binding protein, whose domain organization is similar to that of phospholipase C-_1 but is catalytically inactive, comprizing two isoforms, PRIP-1 and PRIP-2. To get insight into the biological functions, we generated the double knockout (DKO) mice of both PRIP-1 and PRIPミ2, followed by the phenotypic analyses. DKO mice grew normally and became fertile. However DKO female exhibited the decreased litter occasion and litter size, indicating the dysfunction of female reproductive system. Then we examined the estrus cycle by cytological analysis of daily vaginal smears, resulting in the irregular cycle in DKO mice. We further noticed that the mutant mice had apparently smaller sized uterus by gross anatomical observation. Basal levels of serum leuteinizing hormone and follicle stimulating hormone were significantly higher in the mutant, the event of which was also confirmed by examining the secretion from the tissue culture of anterior pituitary glands. These results suggest that PRIP is involved in maternal reproduction, through the gonadotropine secretion..
Membership in Academic Society
  • The Molecular Biology Society of Japan
  • The Japanese biochemical Society
Educational