keyword
https://read.qxmd.com/read/38474382/hedgehog-on-the-move-glypican-regulated-transport-and-gradient-formation-in-drosophila
#21
REVIEW
Carlos Jiménez-Jiménez, Kay Grobe, Isabel Guerrero
Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), among others. In the Hh-signalling pathway, Glps have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix, and for unimpaired ligand reception in distant recipient cells...
February 27, 2024: Cells
https://read.qxmd.com/read/38474342/collagen-vi-deficiency-impairs-tendon-fibroblasts-mechanoresponse-in-ullrich-congenital-muscular-dystrophy
#22
JOURNAL ARTICLE
Vittoria Cenni, Patrizia Sabatelli, Alberto Di Martino, Luciano Merlini, Manuela Antoniel, Stefano Squarzoni, Simona Neri, Spartaco Santi, Samuele Metti, Paolo Bonaldo, Cesare Faldini
The pericellular matrix (PCM) is a specialized extracellular matrix that surrounds cells. Interactions with the PCM enable the cells to sense and respond to mechanical signals, triggering a proper adaptive response. Collagen VI is a component of muscle and tendon PCM. Mutations in collagen VI genes cause a distinctive group of inherited skeletal muscle diseases, and Ullrich congenital muscular dystrophy (UCMD) is the most severe form. In addition to muscle weakness, UCMD patients show structural and functional changes of the tendon PCM...
February 22, 2024: Cells
https://read.qxmd.com/read/38468970/activated-hedgehog-gene-pattern-correlates-with-dismal-clinical-outcome-and-tumor-microenvironment-heterogeneity-in-hepatocellular-carcinoma
#23
JOURNAL ARTICLE
Limin Zhen, Yi Zhu, Zhen Wu, Jinyao Liao, Liaoyuan Deng, Qianqian Ma, Qili Wu, Gang Ning, Qiuxiong Lin, Liya Zhou, Yanjie Huang, Zewei Zhuo, Ren Chen, Dongnan Yu
BACKGROUND: Activation of the Hedgehog signaling pathway is linked to the initiation and development of human hepatocellular carcinoma (HCC). However, its impact on clinical outcomes and the HCC microenvironment remains unclear. METHODS: We performed comprehensive analyses of Hedgehog pathway genes in a large cohort of HCC patients. Specifically, we utilized univariate Cox regression analysis to identify Hedgehog genes linked to overall survival, and the LASSO algorithm was used to construct a Hedgehog-related gene pattern...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38464967/re-analysis-of-gene-mutations-found-in-pituitary-stalk-interruption-syndrome-and-a-new-hypothesis-on-the-etiology
#24
JOURNAL ARTICLE
Shengjie Wang, Qiaozhen Qin, Deyue Jiang, Yan Xiao, Lingtong Ye, Xiaoxia Jiang, Qinghua Guo
BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory...
2024: Frontiers in Endocrinology
https://read.qxmd.com/read/38457499/activation-of-cgrp-receptor-mediated-signaling-promotes-tendon-bone-healing
#25
JOURNAL ARTICLE
Xibang Zhao, Guanfu Wu, Jing Zhang, Ziyi Yu, Jiali Wang
Calcitonin gene-related peptide (CGRP), an osteopromotive neurotransmitter with a short half-life, shows increase while calcitonin receptor-like (CALCRL) level is decreased at the early stage in bone fractures. Therefore, the activation of CALCRL-mediated signaling may be more critical to promote the tendon-bone healing. We found CGRP enhanced osteogenic differentiation of BMSCs through PKA/CREB/JUNB pathway, contributing to improved sonic hedgehog (SHH) expression, which was verified at the tendon-bone interface (TBI) in the mice with Calcrl overexpression...
March 8, 2024: Science Advances
https://read.qxmd.com/read/38453756/targeting-triple-negative-breast-cancer-stem-cells-using-nanocarriers
#26
REVIEW
Nagasen Dasari, Girija Sankar Guntuku, Sai Kiran S S Pindiprolu
Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, and treatment responses. Categorization of subtypes is based on the presence or absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), leading to subtypes such as luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). TNBC, comprising around 20% of all breast cancers, lacks expression of ER, PR, and HER2 receptors, rendering it unresponsive to targeted therapies and presenting significant challenges in treatment...
March 7, 2024: Discov Nano
https://read.qxmd.com/read/38453045/tgf-%C3%AE-1-smad3-driven-gli2-isoform-expression-contributes-to-aggressive-phenotypes-of-hepatocellular-carcinoma
#27
JOURNAL ARTICLE
Jia Ding, Yong-Yu Yang, Peng-Tao Li, Yue Ma, Li Zhang, Yuan Zhou, Cheng Jin, Hui-Yan Li, Yuan-Fei Zhu, Xiu-Ping Liu, Zheng-Jin Liu, Hu-Liang Jia, Ping-Guo Liu, Jian Wu
Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-β1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-β1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells...
March 5, 2024: Cancer Letters
https://read.qxmd.com/read/38451311/bmp4-and-grem1-are-targets-of-shh-signaling-and-downstream-regulators-of-collagen-in-the-penis
#28
JOURNAL ARTICLE
Jiangping Deng, Timothy Searl, Samuel Ohlander, Danuta Dynda, Daniel A Harrington, Kevin T McVary, Carol A Podlasek
BACKGROUND: Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. AIM: We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment...
March 6, 2024: Journal of Sexual Medicine
https://read.qxmd.com/read/38442710/a-sterol-analog-inhibits-hedgehog-pathway-by-blocking-cholesterylation-of-smoothened
#29
JOURNAL ARTICLE
Yuan-Bin Liu, Li-Ming He, Ming Sun, Wen-Jun Luo, Zi-Cun Lin, Zhi-Ping Qiu, Yu-Liang Zhang, Ao Hu, Jie Luo, Wen-Wei Qiu, Bao-Liang Song
The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation...
February 28, 2024: Cell Chemical Biology
https://read.qxmd.com/read/38438324/ire1%C3%AE-inhibits-osteogenic-differentiation-of-mouse-embryonic-fibroblasts-by-limiting-shh-signaling
#30
JOURNAL ARTICLE
Zhixiang Zhang, Xuan Zhang, Xiangzhen Wei, Chengbo Yu, Li Xiao, Jianmiao Liu, Yong Liu, Yingguang Cao, Ke Song
OBJECTIVES: This study aimed to investigate the effect of endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) on the sonic hedgehog N-terminus (N-Shh)-enhanced-osteogenic differentiation process in mouse embryonic fibroblasts (MEFs). MATERIALS AND METHODS: Osteogenesis of MEFs was observed by alkaline phosphatase (ALP) staining, alizarin red staining, and Von Kossa staining assays. Activation of unfolded protein response and Shh signaling were examined using real-time quantitative PCR and western blot assays...
March 4, 2024: Oral Diseases
https://read.qxmd.com/read/38433280/nf-%C3%AE%C2%BAb-in-biology-and-targeted-therapy-new-insights-and-translational-implications
#31
REVIEW
Qing Guo, Yizi Jin, Xinyu Chen, Xiaomin Ye, Xin Shen, Mingxi Lin, Cheng Zeng, Teng Zhou, Jian Zhang
NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling...
March 4, 2024: Signal Transduction and Targeted Therapy
https://read.qxmd.com/read/38432565/beyond-cyclopamine-targeting-hedgehog-signaling-for-cancer-intervention
#32
REVIEW
Beena Thazhackavayal Baby, Aniruddha Murahar Kulkarni, Prasanna Kumar Reddy Gayam, Kuzhuvelil B Harikumar, Jesil Mathew Aranjani
Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at...
March 1, 2024: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/38418183/-en1-promotes-cell-proliferation-and-migration-via-hedgehog-signaling-pathway-in-esophageal-squamous-cell-carcinoma
#33
JOURNAL ARTICLE
N Zhao, T Y Gong, Z C Wei, J Cong, Z H Liu, H Y Chen
Objective: To explore the function and mechanism of transcription factor En1 in esophageal squamous cell carcinoma (ESCC). Methods: The correlations of En1 with prognosis were analyzed using the overall survival data of 9 397 pan-cancer patients and progression-free survival data of 4 349 pan-cancer patients from The Cancer Genome Atlas (TCGA) database. The En1 expression data in 53 and 155 cases of ESCC and their paired adjacent tissues were from Gene Expression Omnibus (GEO) database and National Genomics Data Center-Genome Sequence Archive(NGDC-GSA)database...
February 23, 2024: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://read.qxmd.com/read/38411252/ptch1-mutant-human-cerebellar-organoids-exhibit-altered-neural-development-and-recapitulate-early-medulloblastoma-tumorigenesis
#34
JOURNAL ARTICLE
Max J van Essen, Elizabeth J Apsley, Joey Riepsaame, Ruijie Xu, Paul A Northcott, Sally A Cowley, John Jacob, Esther B E Becker
Patched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development...
February 1, 2024: Disease Models & Mechanisms
https://read.qxmd.com/read/38409358/elucidating-hedgehog-pathway-s-role-in-hnscc-progression-insights-from-a-6-gene-signature
#35
JOURNAL ARTICLE
Yang Yang, Chenxi Yang, Qiying Yang, Shun Lu, Bisheng Liu, Dongyun Li, Dongliang Li, Peng Zhang, Peng Xu, Jinyi Lang, Jie Zhou
With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model...
February 26, 2024: Scientific Reports
https://read.qxmd.com/read/38383071/temporal-gene-signature-of-myofibroblast-transformation-in-peyronie-s-disease-first-insights-into-the-molecular-mechanisms-of-irreversibility
#36
JOURNAL ARTICLE
Marcus M Ilg, Sophie Harding, Alice R Lapthorn, Sara Kirvell, David J Ralph, Stephen A Bustin, Graham Ball, Selim Cellek
BACKGROUND: Transformation of resident fibroblasts to profibrotic myofibroblasts in the tunica albuginea is a critical step in the pathophysiology of Peyronie's disease (PD). We have previously shown that myofibroblasts do not revert to the fibroblast phenotype and we suggested that there is a point of no return at 36 hours after induction of the transformation. However, the molecular mechanisms that drive this proposed irreversibility are not known. AIM: Identify molecular pathways that drive the irreversibility of myofibroblast transformation by analyzing the expression of the genes involved in the process in a temporal fashion...
February 21, 2024: Journal of Sexual Medicine
https://read.qxmd.com/read/38372724/genetic-screen-identified-prmt5-as-a-neuroprotection-target-against-cerebral-ischemia
#37
JOURNAL ARTICLE
Haoyang Wu, Peiyuan Lv, Jinyu Wang, Brian Bennett, Jiajia Wang, Pishun Li, Yi Peng, Guang Hu, Jiaji Lin
Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo...
February 19, 2024: ELife
https://read.qxmd.com/read/38370230/exploring-candidate-genes-for-heat-tolerance-in-ovine-through-liver-gene-expression
#38
JOURNAL ARTICLE
Messy Hannear de Andrade Pantoja, Francisco José de Novais, Gerson Barreto Mourão, Raluca G Mateescu, Mirele Daiana Poleti, Mariane Beline, Camylla Pedrosa Monteiro, Heidge Fukumasu, Cristiane Gonçalves Titto
Thermotolerance has become an essential factor in the prevention of the adverse effects of heat stress, but it varies among animals. Identifying genes related to heat adaptability traits is important for improving thermotolerance and for selecting more productive animals in hot environments. The primary objective of this research was to find candidate genes in the liver that play a crucial role in the heat stress response of Santa Ines sheep, which exhibit varying levels of heat tolerance. To achieve this goal, 80 sheep were selected based on their thermotolerance and placed in a climate chamber for 10 days, during which the average temperature was maintained at 36 °C from 10 a...
February 29, 2024: Heliyon
https://read.qxmd.com/read/38369829/-advances-in-the-biological-characteristics-and-stem-maintenance-mechanisms-of-tumor-stem-cells
#39
JOURNAL ARTICLE
Wenjing Zhang, Kexu Zhao, Keyue Zhang, Xiaoyang Chen, Mingxuan Hao, Zhao Yang
Tumor is one of the most serious diseases that threaten human health and social development, and it is the second most common cause of death worldwide. The latest statistics show that malignant tumors have surpassed cardiovascular disease as the leading cause of death in developed countries. Drug resistance, metastasis, and recurrence of tumors continue to present urgent challenges in clinical treatment. Tumor stem cells (TSCs) are a specific subset of cells that possess high capabilities of self-renewal, differentiation potential, tumorigenicity and drug resistance...
February 25, 2024: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://read.qxmd.com/read/38366037/emerging-mechanistic-understanding-of-cilia-function-in-cellular-signalling
#40
REVIEW
Keren I Hilgendorf, Benjamin R Myers, Jeremy F Reiter
Primary cilia are solitary, immotile sensory organelles present on most cells in the body that participate broadly in human health, physiology and disease. Cilia generate a unique environment for signal transduction with tight control of protein, lipid and second messenger concentrations within a relatively small compartment, enabling reception, transmission and integration of biological information. In this Review, we discuss how cilia function as signalling hubs in cell-cell communication using three signalling pathways as examples: ciliary G-protein-coupled receptors (GPCRs), the Hedgehog (Hh) pathway and polycystin ion channels...
February 16, 2024: Nature Reviews. Molecular Cell Biology
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