Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
K. M. Diguilio, E. Rybakovsky, M. C. Valenzano, H. H. Nguyen, E. A. Del Rio, E. Newberry, R. Spadea, J. M. Mullin
Summary: The study found that quercetin can improve airway epithelial cell barrier function and reduce barrier compromise caused by TNF-α. This improvement may be related to changes in tight junctional protein composition and inhibition of cell replication.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Multidisciplinary Sciences
Erika Wakayama, Taiki Kuzu, Keisuke Tachibana, Ryuichi Hirayama, Yoshiaki Okada, Masuo Kondoh
Summary: The blood-brain barrier poses a challenge to drug delivery to the central nervous system. Among the components of the tight junctions in the blood-brain barrier, claudin-5 has been studied extensively as a target for enhancing drug permeation into the brain. However, sustained knockdown of claudin-5 is lethal in mice and administration of an anti-claudin-5 antibody can cause convulsions in nonhuman primates.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jong-Chan Ahn, Su Jung Hwang, Hyo-Jong Lee, Kyu-Won Kim
Summary: The study showed that claudin-5a is crucial for establishing and maintaining the blood-neural barrier during zebrafish development. Knockdown of claudin-5a resulted in selective leakage through the BBB, decreased expression of glucose transporter 1 in cerebral microvessels, and leakiness in the blood-cerebrospinal fluid barrier, indicating overall abnormal development of the blood-neural barriers.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Clinical Neurology
Yosuke Hashimoto, Karine Poirier, Nathalie Boddaert, Laurence Hubert, Melodie Aubart, Anna Kaminska, Marianne Alison, Isabelle Desguerre, Arnold Munnich, Matthew Campbell
Summary: This study reports a novel mutation in the CLDN5 gene associated with alternating hemiplegia with microcephaly. The mutation leads to the conversion of the blood-brain barrier into an anion-selective channel, indicating that CLDN5 associated alternating hemiplegia is a channelopathy.
Article
Food Science & Technology
Lucas Heils, Martina Schneemann, Ralf Gerhard, Joerg-Dieter Schulzke, Roland Buecker
Summary: The study investigated the impact of Clostridioides difficile binary toxin (CDT) on the intestinal epithelial barrier and found that sublethal concentrations of CDT induced barrier dysfunction with increased permeability and redistribution of tight junction proteins. This suggests that CDT may contribute to diarrhea by compromising the intestinal barrier function.
Article
Ophthalmology
Aihua Hou, Safiah Mohamed Ali, Evelyn Png, Walter Hunziker, Louis Tong
Summary: The purpose of this study was to investigate the role of TG-2 in corneal barrier function and its regulation of epithelial junctional proteins and transcription factors. Corneas from TG-2-/- mice showed lower trans-epithelial electrical resistance and increased central corneal thickness compared to TG-2+/+ mice. TG-2-/- mice also exhibited a faster increase in fluorescence in the anterior chamber after ocular exposure to FITC-dextran. The expression of Claudin-1 protein and transcript levels were reduced in the cornea of TG-2-/- mice and in TG-2 knockdown human corneal epithelial cells.
Article
Dermatology
Mika Fujikawa, Hiroko Sugimoto, Rie Tamura, Koki Fujikawa, Ami Yamagishi, Yuhki Ueda
Summary: The moisturizing agent MPS can repair TJ barrier dysfunction and improve the reduction caused by histamine in AD patients, suggesting it as a new therapeutic option.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katherine M. DiGuilio, Elizabeth Rybakovsky, Reza Abdavies, Romy Chamoun, Colleen A. Flounders, Ariel Shepley-McTaggart, Ronald N. Harty, James M. Mullin
Summary: Existing literature strongly supports the association between disease morbidity and epithelial barrier leak, as well as the role of micronutrients in reducing barrier leak. Zinc, Vitamin A, and Vitamin D can induce molecular changes that reduce barrier leak at elevated dosages, potentially serving as adjuvant therapeutics in disease management, particularly in light of the COVID-19 pandemic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
Yunika Mayangsari, Mayu Okudaira, Chinatsu Mano, Yuki Tanaka, Osamu Ueda, Tomohiro Sakuta, Yoshiharu Suzuki, Yoshinari Yamamoto, Takuya Suzuki
Summary: Research showed that DMF can enhance intestinal TJ barrier integrity by increasing the expression of occludin and claudin-1, while reducing the expression of claudin-2. This regulation involves the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Veterinary Sciences
Ruibiao Wang, Yuheng Zhang, Jingbo Zhen, Jinpeng Zhang, Zixuan Pang, Xuewei Song, Lihao Lin, Feng Sun, Yixin Lu
Summary: This study explored the effect of exosomes derived from Trichinella spiralis infective larvae (TsExos) on the barrier function of porcine small intestinal epithelial cells (IPEC-J2). The results showed that TsExos ingestion decreased cell viability, increased FITC-dextran content, lactate dehydrogenase and reactive oxygen species levels. TsExos also induced apoptosis, nuclear pyknosis, and nuclear rupture. In addition, TsExos disrupted tight junctions and altered gene expression.
VETERINARY RESEARCH
(2022)
Article
Food Science & Technology
Sefat E. Khuda, Ann V. Nguyen, Girdhari M. Sharma, Mohammad S. Alam, Kannan V. Balan, Kristina M. Williams
Summary: This study found that polysorbate-80 may enhance the absorption of allergens in a size-dependent manner by modulating paracellular permeability.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Ashley Monaco, Ben Ovryn, Josephine Axis, Kurt Amsler
Summary: The paracellular permeability in epithelial cells involves both a Pore Pathway for small ions and solutes, and a Leak Pathway for larger solutes. While the Pore Pathway is better understood, the proteins and mechanism behind the Leak Pathway remain unresolved and controversial. Further research is needed to clarify the molecular basis and regulation of the Leak Pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Roziana Kamaludin, Zatilfarihiah Rasdi, Mohd Hafiz Dzarfan Othman, Siti Hamimah Sheikh Abdul Kadir, Mohd Yusri Idorus, Jesmine Khan, Wan Nor I'zzah Wan Mohamad Zain, Ahmad Fauzi Ismail, Mukhlis A. Rahman, Juhana Jaafar
Summary: This study found that BPA exposure can affect the small intestine and intestinal barrier of pregnant rats and their fetuses, but BPA-treated water through photocatalytic membrane does not have detrimental effects on the gastrointestinal tract.
Article
Gastroenterology & Hepatology
Luz del Carmen Martinez-Sanchez, Phuong Anh Ngo, Rashmita Pradhan, Lukas-Sebastian Becker, David Boehringer, Despina Soteriou, Marketa Kubankova, Christine Schweitzer, Tatyana Koch, Veronika Thonn, Lena Erkert, Iris Stolzer, Claudia Guenther, Christoph Becker, Benno Weigmann, Monika Klewer, Christoph Daniel, Kerstin Amann, Stefan Tenzer, Raja Atreya, Martin Bergo, Cord Brakebusch, Alastair J. M. Watson, Jochen Guck, Ben Fabry, Imke Atreya, Markus F. Neurath, Rocio Lopez-Posadas
Summary: Abnormal cell shedding is associated with intestinal barrier dysfunction and inflammatory bowel diseases. Deletion of PGGTase and RAC1 in intestinal epithelial cells leads to cell overcrowding and epithelial leakage, resulting in chronic intestinal inflammation. RAC1 plays a crucial role in regulating cytoskeletal dynamics, cell mechanics, and intestinal cell shedding.
Article
Cell Biology
Kenta Shigetomi, Yumiko Ono, Tetsuichiro Inai, Junichi Ikenouchi
JOURNAL OF CELL BIOLOGY
(2018)
Review
Biochemistry & Molecular Biology
Kenta Shigetomi, Junichi Ikenouchi
Article
Cell Biology
Kana Aoki, Shinsuke Satoi, Shota Harada, Seiichi Uchida, Yoh Iwasa, Junichi Ikenouchi
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Multidisciplinary Sciences
Kana Aoki, Shota Harada, Keita Kawaji, Kenji Matsuzawa, Seiichi Uchida, Junichi Ikenouchi
Summary: The cytoplasm in mammalian cells is considered homogeneous. Here authors report that the cytoplasmic fluidity is regulated in the blebbing cells, which is regulated by calcium concentration in the expanding blebs and involves the STIM-Orai1 pathway.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Kenji Matsuzawa, Hayato Ohga, Kenta Shigetomi, Tomohiro Shiiya, Masanori Hirashima, Junichi Ikenouchi
Summary: The study demonstrates that MAGI proteins regulate apical constriction of epithelial cells by modulating the distribution of Par polarity proteins, thereby maintaining steady state intercellular tension throughout the epithelial cell sheet.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Junichi Ikenouchi, Kana Aoki
Summary: When the plasma membrane detaches from the underlying actin cortex, it expands to form a spherical membrane protrusion called a bleb. The bleb retracts when the actin cortex is reassembled. Many unanswered questions remain regarding membrane source, actin reassembly signals, and cytoplasmic fluidity regulation during bleb formation. Additionally, the use of blebs by cancer cells for invasion and the coordination of molecules involved in bleb formation, expansion, and retraction for directional migration are areas of little current knowledge. In this review, molecular mechanisms of bleb regulation are discussed based on various experimental systems.
Article
Cell Biology
Yuma Cho, Daichi Haraguchi, Kenta Shigetomi, Kenji Matsuzawa, Seiichi Uchida, Junichi Ikenouchi
Summary: This study revealed the role of tricellulin in regulating actomyosin organization at tricellular junctions, contributing to the formation of the epithelial barrier. Additionally, alpha-catenin was identified as a novel binding partner of tricellulin, bridging tricellulin attachment to actin cables and closing the gap at tricellular junctions.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Yumiko Ono, Kenji Matsuzawa, Junichi Ikenouchi
Summary: This study reveals that epithelial cells selectively expand the apical membrane and maintain plasma membrane tension in hypo-osmotic stress through the activation of mTORC2-Rab35 axis, which enhances the transport of secretory vesicles containing major lipid to the apical membrane.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kenta Shigetomi, Yumiko Ono, Kenji Matsuzawa, Junichi Ikenouchi
Summary: It has been found that cholesterol accumulation is essential for the formation of tight junctions, which are crucial for the epithelial barrier. Despite the absence of tight junctions, cholesterol still accumulates normally in the vicinity of the apical junctions. Moreover, a claudin mutant that cannot bind to Zonula Occludens (ZO) proteins can still form tight junction strands. ZO proteins are not only scaffolds for claudins, but also promote the formation of cholesterol-rich membrane domains at apical junctions through their effect on the junctional actomyosin cytoskeleton.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Yuki Fujii, Junichi Ikenouchi
Summary: Blebs are membrane structures formed by detachment of the plasma membrane from the underlying actin cytoskeleton. Recent studies have revealed the importance of cytoplasmic zoning in bleb expansion.
JOURNAL OF BIOCHEMISTRY
(2023)