7,045 results match your criteria hedgehog pathway


E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.

J Cell Biol 2021 Sep 23;220(9). Epub 2021 Jun 23.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.

The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. Read More

View Article and Full-Text PDF
September 2021

Localized chondro-ossification underlies joint dysfunction and motor deficits in the mouse model of osteogenesis imperfecta.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;

Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that loss-of-function mutations in FK506 Binding Protein 10 () lead to skeletal deformities in conjunction with joint contractures. However, the pathogenic mechanisms underlying joint dysfunction in OI are poorly understood. Read More

View Article and Full-Text PDF

Itraconazole in the treatment of basal cell carcinoma: A case-based review of the literature.

Australas J Dermatol 2021 Jun 23. Epub 2021 Jun 23.

Skin Specialist Centre, Auckland, New Zealand.

Itraconazole is as an anti-fungal agent with the ability to inhibit the Hedgehog signalling pathway, which makes it a candidate drug that can be repurposed for the treatment of basal cell carcinomas (BCCs). We present a case of metastatic BCC, treated with oral itraconazole 100 mg twice daily, that resulted in sustained partial regression of metastatic pulmonary nodules. A systematic review on the clinical outcomes of BCCs treated with itraconazole highlights that current evidence for its clinical application remains limited and that this is the first case report where itraconazole monotherapy has achieved favourable response in metastatic BCC. Read More

View Article and Full-Text PDF

WISP-1 induced by mechanical stress contributes to fibrosis and hypertrophy of the ligamentum flavum through Hedgehog-Gli1 signaling.

Exp Mol Med 2021 Jun 22. Epub 2021 Jun 22.

Department of Spine Surgery, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, China.

Ongoing chronic fibrosis and hypertrophy of the ligamentum flavum (LF) is an important cause of lumbar spinal canal stenosis (LSCS). Our previous work showed that WNT1-inducible signaling pathway protein 1 (WISP-1) is a critical driver of LF fibrosis. However, the potential mechanism has not been explored. Read More

View Article and Full-Text PDF

Lasting response after discontinuation of Cemiplimab in a patient with locally advanced basal cell carcinoma.

Clin Exp Dermatol 2021 Jun 22. Epub 2021 Jun 22.

Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.

Basal cell carcinoma (BCC) is the most common skin malignancy in humans. Most of the cases can be cured through complete surgical excision as recommended by international guidelines. However, a minority of BCCs progress to a locally advanced (laBCC) or metastatic form and in these late stages, surgery is not indicated as it is not effective. Read More

View Article and Full-Text PDF

A review of emerging and non-US FDA-approved topical agents for the treatment of basal cell carcinoma.

Future Oncol 2021 Jun 22. Epub 2021 Jun 22.

Department of Dermatology, University of Texas McGovern Medical School at Houston, Houston, TX 77030, USA.

Although surgical therapy continues to be the gold standard for the treatment of basal cell carcinoma given high cure rates and the ability to histologically confirm tumor clearance, there are a number of nonsurgical treatment options that may be considered based on individual tumor characteristics, functional and cosmetic considerations, patient comorbidities and patient preference. Topical 5-fluorouracil 5% cream and imiquimod 5% cream have been US FDA-approved for the treatment of superficial basal cell carcinoma. Additionally, a number of new and emerging topical agents and techniques have been described for the treatment of basal cell carcinoma and will be reviewed herein. Read More

View Article and Full-Text PDF

Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy.

J Cell Mol Med 2021 Jun 21. Epub 2021 Jun 21.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti-inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)-induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. Read More

View Article and Full-Text PDF

Systemic hedgehog inhibitors to treat locally advanced basal cell carcinomas of the head-neck region: a retrospective study.

Dermatol Ther 2021 Jun 21:e15036. Epub 2021 Jun 21.

Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

View Article and Full-Text PDF

Beta1-integrin/Hedgehog-Gli1 signaling pathway fuels the diameter-dependent osteoblast differentiation on different TiO nanotubes: The optimal-diameter nanotubes for osteoblast differentiation.

Int J Biochem Cell Biol 2021 Jun 17:106026. Epub 2021 Jun 17.

The Department of Stomatology, Jieyang Affiliated Hospital, Sun Yat-sen University, Jieyang, Guangdong, China. Electronic address:

Micro/nanotextured topographies (MNTs) can modulate cell-biomaterial interactions mostly by their controllable geometrics. Among them, TiO nanotubes, regarded as having a highly controllable nanoscale geometry, have been extensively investigated and applied and significantly affect diameter-dependent cell biological behaviors. In this study, we used five typical MNTs decorated with TiO nanotubes with diameters of 30, 50, 70, 100 and 120 nm to explore the optimal nanotube diameter for improving the biofunctional properties and to more deeply understand the underlying mechanisms by which these MNTs affect osteogenic differentiation by revealing the effect of beta1-integrin/Hedgehog-Gli1 signaling on this process. Read More

View Article and Full-Text PDF

Induction of Ventral Spinal V0 Interneurons from Mouse Embryonic Stem Cells.

Stem Cells Dev 2021 Jun 17. Epub 2021 Jun 17.

The University of Texas at Austin, Biomedical Engineering, 107 W Dean Keeton St., BME 3.314, Austin, Texas, United States, 78712;

The ventral spinal population of V0 interneurons (INs) contribute to the coordinated movements directed by spinal central pattern generators (CPGs), including respiratory circuits and left-right alternation in locomotion. One challenge in studying V0 INs has been the limited number of cells that can be isolated from primary sources for basic research or therapeutic use. However, derivation from a pluripotent source, such as has been done recently for other IN populations, could resolve this issue. Read More

View Article and Full-Text PDF

Nanoparticles as a Hedgehog signaling inhibitor for the suppression of cancer growth and metastasis.

Nanoscale 2021 Jun 17. Epub 2021 Jun 17.

Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.

Nanoparticles (NPs) have been intensively explored for the treatment of tumors during the past decade, yet little information has been provided on the NPs' inherent therapeutic activity against cancers. With this goal in mind, we reveal that biocompatible silicon (Si) NPs (SiNPs) feature excellent anti-growth and anti-metastasis activities against prostate cancer cells that show aberrant activation of the Hedgehog (HH) signaling pathway. Without activation by the Sonic hedgehog (Shh)-agonist, mouse embryonic fibroblast (NIH3T3) cells show no response to SiNP exposure. Read More

View Article and Full-Text PDF

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing.

Cell Death Dis 2021 Jun 16;12(7):625. Epub 2021 Jun 16.

Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, 95123, Catania, Italy.

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. Read More

View Article and Full-Text PDF

Downregulated luteolytic pathways in the transcriptome of early pregnancy bovine corpus luteum are mimicked by interferon-tau in vitro.

BMC Genomics 2021 Jun 16;22(1):452. Epub 2021 Jun 16.

Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 7610001, Rehovot, Israel.

Background: Maintenance of the corpus luteum (CL) beyond the time of luteolysis is essential for establishing pregnancy. Identifying the distinct features of early pregnancy CL remains unresolved, hence we analyzed here the transcriptome of CL on day 18 pregnant (P) and non-pregnant (NP) cows using RNA-Seq. CL of P cows expressed ISGs, verifying exposure to the pregnancy recognition signal, interferon-tau (IFNT), whereas the CL of NP cows had elevated luteal progesterone levels, implying that luteolysis had not yet commenced. Read More

View Article and Full-Text PDF

PHF19 activates Hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma.

Exp Cell Res 2021 Jun 12:112690. Epub 2021 Jun 12.

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. Read More

View Article and Full-Text PDF

Hedgehog transcriptional effector GLI mediates mTOR-Induced PD-L1 expression in gastric cancer organoids.

Cancer Lett 2021 Jun 12;518:59-71. Epub 2021 Jun 12.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA. Electronic address:

Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8 cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. Read More

View Article and Full-Text PDF

Activation of AMPK sensitizes medulloblastoma to Vismodegib and overcomes Vismodegib-resistance.

FASEB Bioadv 2021 Jun 17;3(6):459-469. Epub 2021 Mar 17.

Department of Medicine Division of Translational Research Roswell Park Comprehensive Cancer Center Buffalo NY USA.

Vismodegib, a Smoothened antagonist, is clinically approved for treatment of human basal cell carcinoma (BCC), in the clinical trials of medulloblastoma (MB) and other cancers. However, a significant proportion of these tumors fail to respond to Vismodegib after a period of treatment. Here, we find that AMPK agonists, A769662, and Metformin, can inhibit GLI1 activity and synergize with Vismodegib to suppress MB cell growth and . Read More

View Article and Full-Text PDF

Corrigendum to "Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health".

Neural Plast 2021 25;2021:9762592. Epub 2021 May 25.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

[This corrects the article DOI: 10.1155/2020/8815195.]. Read More

View Article and Full-Text PDF

Constitutive Hedgehog/GLI2 signaling drives extracutaneous basaloid squamous cell carcinoma development and bone remodeling.

Carcinogenesis 2021 Jun 12. Epub 2021 Jun 12.

Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.

Uncontrolled activation of the Hedgehog (Hh) signaling pathway, operating through GLI transcription factors, plays a central role in the pathogenesis of cutaneous basal cell carcinoma and contributes to the development of several malignancies arising in extracutaneous sites. We now report that K5-tTA;tetO-Gli2 bitransgenic mice develop distinctive epithelial tumors within their jaws. These tumors consist of large masses of highly proliferative, monomorphous, basaloid cells with scattered foci of keratinization and central necrosis, mimicking human basaloid squamous cell carcinoma (BSCC), an aggressive upper aerodigestive tract tumor. Read More

View Article and Full-Text PDF

Medicinal chemistry of anthranilic acid derivatives: A mini review.

Drug Dev Res 2021 Jun 12. Epub 2021 Jun 12.

Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab, India.

Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti-inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. Read More

View Article and Full-Text PDF

Resveratrol-mediated neurorestoration after cerebral ischemic injury - Sonic Hedgehog signaling pathway.

Life Sci 2021 Jun 8;280:119715. Epub 2021 Jun 8.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Aims: Resveratrol pretreatment can decrease ischemic cerebral injury and enhance proliferation of neural stem cells via mediation of Sonic Hedgehog signaling. However, it is relatively little known about whether neurorestorative effects of resveratrol are mediated by Shh signaling in ischemic cerebral injury. The present study tests whether the Shh signaling pathway mediates resveratrol to promote neurorestoration of ischemic cerebral injury. Read More

View Article and Full-Text PDF

GLI1: A Therapeutic Target for Cancer.

Front Oncol 2021 25;11:673154. Epub 2021 May 25.

Oncology Department, Drug Discovery Division, Southern Research, Birmingham, AL, United States.

GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1 has been linked to the promotion of numerous hallmarks of cancer, such as proliferation, survival, angiogenesis, metastasis, metabolic rewiring, and chemotherapeutic resistance. All of these are driven, in part, by GLI1's role in regulating cell cycle, DNA replication and DNA damage repair processes. Read More

View Article and Full-Text PDF

Sterol regulation of developmental and oncogenic Hedgehog signaling.

Biochem Pharmacol 2021 Jun 7:114647. Epub 2021 Jun 7.

Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

The Hedgehog (Hh) family of lipid-modified signaling proteins directs embryonic tissue patterning and postembryonic tissue homeostasis, and dysregulated Hh signaling drives familial and sporadic cancers. Hh ligands bind to and inhibit the tumor suppressor Patched and allow the oncoprotein Smoothened (SMO) to accumulate in cilia, which in turn activates the GLI family of transcription factors. Recent work has demonstrated that endogenous cholesterol and oxidized cholesterol derivatives (oxysterols) bind and modulate SMO activity. Read More

View Article and Full-Text PDF

Sonic Hedgehog Pathway Blockade After Surgical Debulk of Large Exophytic Basal Cell Carcinomas.

Dermatol Surg 2021 Jun 7. Epub 2021 Jun 7.

Department of Dermatology, The Milton S. Hershey Medical Center, Hershey, Pennsylvania Department of Dermatology, Cleveland Clinic, Cleveland, Ohio.

View Article and Full-Text PDF

A high level of KLF12 causes folic acid-resistant neural tube defects by activating the Shh signalling pathway in mice.

Biol Reprod 2021 Jun 8. Epub 2021 Jun 8.

Reproductive Medicine Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, People's Republic of China.

Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. Read More

View Article and Full-Text PDF

Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu).

Stem Cell Res Ther 2021 Jun 7;12(1):331. Epub 2021 Jun 7.

Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.

Background: Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH. Read More

View Article and Full-Text PDF

Nkx2-2 expressing taste cells in endoderm-derived taste papillae are committed to the type III lineage.

Dev Biol 2021 Jun 5;477:232-240. Epub 2021 Jun 5.

Monell Chemical Senses Center, Philadelphia, PA, USA.

In mammals, multiple cell-signaling pathways and transcription factors regulate development of the embryonic taste system and turnover of taste cells in the adult stage. Using single-cell RNA-Seq of mouse taste cells, we found that the homeobox-containing transcription factor Nkx2-2, a target of the Sonic Hedgehog pathway and a key regulator of the development and regeneration of multiple cell types in the body, is highly expressed in type III taste cells but not in type II or taste stem cells. Using in situ hybridization and immunostaining, we confirmed that Nkx2-2 is expressed specifically in type III taste cells in the endoderm-derived circumvallate and foliate taste papillae but not in the ectoderm-derived fungiform papillae. Read More

View Article and Full-Text PDF

Investigative Landscape in Advanced Non-Melanoma Skin Cancers.

Curr Treat Options Oncol 2021 Jun 7;22(7):56. Epub 2021 Jun 7.

Department of Oncology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.

Opinion Statement: Advanced non-melanoma skin cancers have been challenging to treat due to limited treatment options. Treatment paradigm has shifted with the approval of immunotherapeutic agents cemiplimab and pembrolizumab which have been a key development and have changed the landscape of advanced or metastatic squamous cell skin cancers. Hedgehog inhibitors, vismodegib and sonidegib, remain upfront options for advanced or metastatic basal cell carcinomas. Read More

View Article and Full-Text PDF

New possible silver lining for pancreatic cancer therapy: Hydrogen sulfide and its donors.

Acta Pharm Sin B 2021 May 31;11(5):1148-1157. Epub 2020 Oct 31.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Read More

View Article and Full-Text PDF

Bone marrow mesenchymal stem cells and their derived exosomes resolve doxorubicin-induced chemobrain: critical role of their miRNA cargo.

Stem Cell Res Ther 2021 Jun 5;12(1):322. Epub 2021 Jun 5.

Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.

Background: Doxorubicin (DOX), a widely used chemotherapeutic agent, can cause neurodegeneration in the brain, which leads to a condition known as chemobrain. In fact, chemobrain is a deteriorating condition which adversely affects the lives of cancer survivors. This study aimed to examine the potential therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) and their derived exosomes (BMSCs-Exo) in DOX-induced chemobrain in rat models. Read More

View Article and Full-Text PDF

Gankyrin activates the hedgehog signalling to drive metastasis in osteosarcoma.

J Cell Mol Med 2021 Jun 5. Epub 2021 Jun 5.

Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Gankyrin is a regulatory subunit of the 26-kD proteasome complex and promotes the occurrence and progression of many malignancies. However, the role of gankyrin in osteosarcoma (OS) metastasis remains unclear. Hedgehog signalling has been shown to regulate stem cell homeostasis and cancer metastasis, but the mechanisms that activate this pathway in OS are still poorly understood. Read More

View Article and Full-Text PDF