Article
Biochemistry & Molecular Biology
Jiaqi Zhou, Lin Lin, Han Cai, Longping Liu, Huarong Wang, Jingwen Zhang, Guoliang Xia, Jianbin Wang, Fengchao Wang, Chao Wang
Summary: This study investigated the role of transcription factor Sp1 in regulating the primordial to primary follicle transition (PPT) in the ovary. Depletion of Sp1 in granulosa cells (GCs) extended mice fertility and reduced PPT, resulting in the preservation of more primordial follicles. Single-cell RNA-seq analysis showed a downregulation of cholesterol metabolism in GC- Sp1 (-/-) mice. Furthermore, promoting PPT by overexpressing ferredoxin-1 (FDX1), a key gene in cholesterol metabolism, or supplementing cholesterol in cultured fetal ovaries.
Article
Biochemistry & Molecular Biology
Antonio Tejera-Munoz, Laura Marquez-Exposito, Lucia Tejedor-Santamaria, Sandra Rayego-Mateos, Macarena Orejudo, Beatriz Suarez-Alvarez, Carlos Lopez-Larrea, Marta Ruiz-Ortega, Raul R. Rodrigues-Diez
Summary: CCN2 plays a role in both fibrotic responses and growth factor-induced oxidative and proinflammatory responses. Its coexistence with TGF-β is necessary for persistent fibrotic response, but the mechanisms involved are not fully understood. CCN2 increases T beta RII expression in VSMCs and maintains TGF-β pathway activation through an EGFR-SMAD dependent manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Developmental Biology
Sarah S. McCarthy, Michele Karolak, Leif Oxburgh
Summary: Expansion of interstitial cells in adult kidney is a hallmark of chronic disease, while their proliferation during fetal development is necessary for organ formation. Inactivation of TGF beta/Smad response in mouse interstitial cell lineage leads to overproliferation of interstitial cells regionally in the kidney medulla. Smad4 loss primarily reduces TGF beta signaling in the interstitium, while increasing Wnt/beta-catenin signaling.
Article
Biochemistry & Molecular Biology
Yan Zhang, Hanbin Wang, Ye Zhu, Xiaojing Hou, Xing Li, Xiaomei Zhou, Lili Ge, Juan Xu, Yiping Su
Summary: Premature ovarian failure (POF) is a complication of ovarian dysfunction caused by the depletion or dysfunction of primordial follicles (PFs). This study identified PFAP1, a peptide that can promote the activation of PFs and restore ovarian function in mice. PFAP1 binds to the protein MCM5, inhibiting its degradation and promoting the proliferation of granulosa cells. These findings suggest that PFAP1 could be a promising therapeutic agent for POF and other ovarian diseases.
Article
Reproductive Biology
Kurumi Fukuda, Masafumi Muraoka, Yuzuru Kato, Yumiko Saga
Summary: The gene expression profile of pre-granulosa cells in mice undergoes significant changes during primordial follicle formation, with oocyte development playing a crucial role in this process.
BIOLOGY OF REPRODUCTION
(2021)
Article
Endocrinology & Metabolism
Juan Feng, Wen-Wen Ma, Hui-Xia Li, Xiu-Ying Pei, Shou-Long Deng, Hua Jia, Wen-Zhi Ma
Summary: This study demonstrates that melatonin (Mel) can serve as an adjuvant to protect young female cancer patients from premature ovarian insufficiency (POI) induced by Cyclophosphaty-45mide (Cyc) chemotherapy. Melatonin treatment maintains ovarian hormone levels and inhibits the mitochondrial apoptotic pathway to prevent follicle loss. This has important implications for preserving fertility in cancer patients undergoing chemotherapy.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Yu Tian, Ming-Yu Zhang, Ai-Hong Zhao, Li Kong, Jun-Jie Wang, Wei Shen, Lan Li
Summary: The study showed that exposure to ZEN alters the developmental trajectory of germ cells and granulosa cells, particularly by disrupting the Hippo signaling pathway, thus affecting the formation of primordial follicles. This research contributes to a deeper understanding of toxicity mechanisms in different cell types and the disruption of normal intercellular signaling caused by ZEN exposure.
Article
Orthopedics
Nathalie G. M. Thielen, Arjan P. M. van Caam, Henk M. V. Beuningen, Elly L. Vitters, Martijn H. J. van den Bosch, Marije I. Koenders, Fons A. J. van de Loo, Esmeralda N. Blaney Davidson, Peter M. van der Kraan
Summary: The study aimed to block TGF-beta-induced SMAD1/5/9 signaling in primary human OA chondrocytes while maintaining functional SMAD2/3 signaling. The results demonstrated that using a low dose of SB-505124 inhibited SMAD1/5/9 phosphorylation and the expression of ID1 and ID3, while maintaining SMAD2/3 phosphorylation and the induction of JUNB and SERPINE1. In addition, TGF-beta regulated hypertrophic and dedifferentiation markers in OA chondrocytes, and blocking only the SMAD1/5/9 pathway showed stronger inhibition on TGF-beta-induced RUNX2 compared to blocking both SMAD pathways.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Review
Cell Biology
Lih-Fhung Hiew, Chi-Him Poon, Heng-Ze You, Lee-Wei Lim
Summary: Research on TGF-beta/Smad signaling has shown its significance in neurogenesis and its potential impact on neuropsychiatric disorders. The relationship between TGF-beta/Smad signaling and neurogenesis in response to stressors suggests a role in stress response regulation and behavioral outcomes of mood disorders. Modifications to these signaling pathways have been found to have diverse effects on neurogenesis, highlighting the complexity of the interactions involved.
Article
Medicine, Research & Experimental
Jun-Jie Wang, Yu Tian, Ming-Hao Li, Yan-Qin Feng, Li Kong, Fa-Li Zhang, Wei Shen
Summary: This study used single-cell RNA sequencing to reveal the gene expression dynamics of female germ and granulosa cells following DEHP exposure in mice. DEHP was found to impede follicle assembly progression in germ cells, inhibit proliferative activity in granulosa cells, disrupt transforming growth factor-beta signaling, and elevate DNA damage and apoptosis in both germ and somatic cells. These findings provide new insights into the reproductive toxicity of DEHP exposure and its impact on ovarian cell interactions.
Article
Oncology
Justin Joseph, Capucine R. Magaut, Simon Storevik, Luiz H. Geraldo, Thomas Mathivet, Md Abdul Latif, Justine Rudewicz, Joris Guyon, Matteo Gambaretti, Frida Haukas, Amalie Trones, Lars A. Romo Ystaas, Jubayer A. Hossain, Sandra Ninzima, Sylvain Cuvellier, Wenjing Zhou, Tushar Tomar, Barbara Klink, Lalit Rane, Bronwyn K. Irving, Joanne Marrison, Peter O'Toole, Heiko Wurdak, Jian Wang, Zhang Di, Even Birkeland, Frode S. Berven, Frank Winkler, Frank A. E. Kruyt, Andreas Bikfalvi, Rolf Bjerkvig, Thomas Daubon, Hrvoje Miletic
Summary: Analysis of TCGA data revealed a high activation of the TGF-beta pathway in GBMs compared to oligodendroglial tumors. Stimulation of GBM cell lines with TGF-beta 1 enhanced MT formation and communication via calcium signaling, while inhibition of the TGF-beta pathway significantly reduced MT formation and invasion. Downstream of TGF-beta, thrombospondin 1 (TSP1) was identified as a potential mediator of MT formation in GBM, which was upregulated upon TGF-beta stimulation and inhibited MT formation when knocked down in vitro and in vivo.
Article
Medicine, Research & Experimental
Alex Boye
Summary: Early detection of cancer is crucial for cancer management and limited survival. Understanding cancer biology and key factors in cancer progression plays a significant role in cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Naohiro Nakamura, Katsunori Yoshida, Rinako Tsuda, Miki Murata, Takashi Yamaguchi, Kanehiko Suwa, Mayuko Ichimura, Koichi Tsuneyama, Koichi Matsuzaki, Toshiaki Nakano, Junko Hirohara, Toshihito Seki, Kazuichi Okazaki, M. Eric Gershwin, Makoto Naganuma
Summary: Patients with primary biliary cholangitis (PBC) are at higher risk for developing hepatocellular carcinoma (HCC), especially in the presence of comorbidities like excessive alcohol consumption. This study found that the balance of Smad signals may serve as a biomarker to predict the likelihood of HCC occurrence in PBC patients. Shifting favorably Smad phospho-isoforms through therapies could potentially reduce the risk of PBC-related HCC development.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Cell Biology
Jung-Chien Cheng, Lanlan Fang, Yang Yan, Jingyan He, Yanjie Guo, Qiongqiong Jia, Yibo Gao, Xiaoyu Han, Ying-Pu Sun
Summary: Estradiol, a main steroid hormone secreted by the ovaries, is crucial for maintaining normal female reproductive function;TGF-beta1 has been shown to stimulate aromatase expression and E2 production in ovarian granulosa cells through the involvement of SMAD2 and ERK1/2 signaling pathways.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Bijun Chen, Ruoshui Li, Silvia C. Hernandez, Anis Hanna, Kai Su, Arti V. Shinde, Nikolaos G. Frangogiannis
Summary: TGF-beta signaling through Smad2/3 regulates macrophage responses in myocardial infarction. Smad3 plays a crucial role in mediating the anti-inflammatory and phagocytic effects of TGF-beta, while the activation of Smad2 does not affect these processes. Smad3, but not Smad2, is the main mediator of transcriptional effects of TGF-beta on macrophages.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Endocrinology & Metabolism
Kate Hardy, Mark Fenwick, Jocelyn Mora, Mhairi Laird, Kacie Thomson, Stephen Franks
Article
Endocrinology & Metabolism
Mhairi Laird, Kacie Thomson, Mark Fenwick, Jocelyn Mora, Stephen Franks, Kate Hardy
Article
Physics, Multidisciplinary
Euan Littlejohns, Carina M. Dunlop
NEW JOURNAL OF PHYSICS
(2018)
Article
Physics, Multidisciplinary
Carina Dunlop
NEW JOURNAL OF PHYSICS
(2019)
Article
Multidisciplinary Sciences
Sofia Granados-Aparici, Kate Hardy, Stephen Franks, Isam B. Sharum, Sarah L. Waite, Mark A. Fenwick
SCIENTIFIC REPORTS
(2019)
Article
Pharmacology & Pharmacy
James W. T. Yates, Helen Byrne, Sonya C. Chapman, Tao Chen, Lourdes Cucurull-Sanchez, Juan Delgado-SanMartin, Giovanni Di Veroli, Simon J. Dovedi, Carina Dunlop, Rajesh Jena, Duncan Jodrell, Emma Martin, Francois Mercier, Antonio Ramos-Montoya, Herbert Struemper, Paolo Vicini
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2020)
Review
Obstetrics & Gynecology
Sallwa M. Alshehre, Brenda F. Narice, Mark A. Fenwick, Mostafa Metwally
Summary: Endometrioma in women undergoing IVF or ICSI leads to a decreased number of oocytes and MII oocytes retrieved, but no significant differences were found in other reproductive outcomes, indicating that IVF/ICSI is a beneficial ART approach for women with endometrioma.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2021)
Article
Multidisciplinary Sciences
Erin A. Henslee, Carina M. Dunlop, Christine M. de Mel, Emily A. Carter, Rula G. Abdallat, Patrizia Camelliti, Fatima H. Labeed
SCIENTIFIC REPORTS
(2020)
Article
Engineering, Biomedical
Thomas I. R. Hopkins, Victoria L. Bemmer, Stephen Franks, Carina Dunlop, Kate Hardy, Iain E. Dunlop
Summary: Follicle development in the ovary is tightly regulated and mechanically influenced, with significant variations in tissue stiffness across different regions. Large developmentally-advanced follicles are found to be mechanically dominant structures in the ovary. This study provides new insights for ovarian biomechanics and follicle tissue engineering.
Article
Biophysics
Josephine Solowiej-Wedderburn, Carina M. Dunlop
Summary: Tissue stiffness plays a crucial role in cell behavior, and the arrangement of adhesions between cells and substrate is also important in determining the effective substrate stiffness experienced by cells. Different adhesion patterns result in equivalent mean cell deformations but different gel stiffnesses. Energy considerations can explain the observed focal adhesion growth and elongation on stiff substrates, as well as the absence of focal adhesions on soft substrates. The simulations suggest that fewer and larger adhesions, randomly placed, are preferred and result in realistic cell shapes.
BIOPHYSICAL JOURNAL
(2022)
Article
Reproductive Biology
Heidy Kaune, Juan F. Montiel, Mark Fenwick, Suzannah A. Williams
Summary: Premature ovarian insufficiency (POI) affects a small percentage of women under 40, and the causes are often unknown. By studying a mouse model of POI, researchers have identified genetic pathways and shared genes that provide new insight into the development of this condition.
REPRODUCTION AND FERTILITY
(2022)
Article
Oncology
Adam Nasim, James Yates, Gianne Derks, Carina Dunlop
Summary: Mathematical models used in preclinical drug discovery are often empirical growth laws, lacking connection with underlying physiologic processes. This study presents a mechanistic model that can predict tumor growth and account for drug distribution effects within tumors. Importantly, the model can be integrated into the current workflow and accurately predict tumor response.
CANCER RESEARCH COMMUNICATIONS
(2022)
Meeting Abstract
Obstetrics & Gynecology
S. Idrees, M. Fenwick, A. Pacey
HUMAN REPRODUCTION
(2019)