Biology subjects

Fujiki, Y.

Publications and source records attributed to Fujiki, Y..

3 recordsLinked to original sources

bioRxiv2022

Novel therapeutic strategies for injured endometrium: Autologous intrauterine transplantation of menstrual blood-derived cells from infertile patients

BackgroundMenstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which needs to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. MethodsWe collected menstrual blood-derived cells from volunteers and infertile patients, and confirmed their mesenchymal stem cell phenotype by flowcytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. ResultsMenstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis and improved fertility outcomes without any apparent complications. ConclusionsIn our preclinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.

cell biology↗

bioRxiv2020

Peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation

Most of peroxisomal matrix proteins including a hydrogen peroxide (H2O2)-decomposing enzyme, catalase, are imported in a peroxisome-targeting signal type-1 (PTS1)-dependent manner. However, little is known about regulation of the membrane-bound protein import machinery. Here, we report that Pex14, a central component of the protein translocation complex in peroxisomal membrane, is phosphorylated in response to oxidative stresses such as H2O2 in mammalian cells. H2O2-induced phosphorylation of Pex14 at Ser232 suppresses peroxisomal import of catalase in vivo and selectively decreases formation of PTS1 receptor Pex5-mediated ternary complex of Pex14 with catalase in vitro. Phosphomimetic Pex14-S232D mutant elevates the level of cytosolic catalase, but not canonical PTS1-proteins, conferring higher cell resistance to H2O2. We thus suggest that H2O2-induced phosphorylation of Pex14 spatiotemporally regulates peroxisomal import of catalase, functioning in counteracting action against oxidative stress by the increase of cytosolic catalase.

cell biology↗

bioRxiv2018

Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis

Summary StatementsWe unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial fission-fusion dynamics, mitochondrion-dependent caspase activation, and cellular apoptosis.\n\nAbstractPeroxisomes cooperate with mitochondria in the performance of cellular metabolic functions such as fatty acid oxidation and maintenance of redox homeostasis. Whether peroxisomes also regulate mitochondrial fission-fusion dynamics or mitochondrion-dependent apoptosis has remained unclear, however. We now show that genetic ablation of the peroxins Pex3 or Pex5, which are essential for peroxisome biogenesis, resulted in mitochondrial fragmentation in mouse embryonic fibroblasts (MEFs) in a manner dependent on dynamin-related protein 1 (Drp1). Conversely, treatment with 4-phenylbutyric acid, an inducer of peroxisome proliferation, resulted in mitochondrial elongation in wild-type MEFs, but not in Pex3-deficient MEFs. We further found that peroxisome deficiency increased the levels of cytosolic cytochrome c and caspase activity under basal conditions without inducing apoptosis. It also greatly enhanced etoposide-induced caspase activation and apoptosis, indicative of an enhanced cellular sensitivity to death signals. Together, our data unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial dynamics and mitochondrion-dependent apoptosis. Given that mutations of peroxin genes are responsible for lethal disorders such as Zellweger syndrome, effects of such mutations on mitochondrion-dependent apoptosis may contribute to disease pathogenesis.

cell biology↗