scholarly journals Sonic hedgehog signaling in epithelial tissue development

2019 ◽  
Vol 7 ◽  
pp. 3
Author(s):  
Lu Zheng ◽  
Chen Rui ◽  
Hao Zhang ◽  
Jing Chen ◽  
Xiuzhi Jia ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Gastric Epithelium ◽  
Epithelial Tissue ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Tissue Repair And Regeneration ◽  
New Treatment

The Sonic hedgehog (SHH) signaling pathway is essential for embryonic development and tissue regeneration. The dysfunction of SHH pathway is involved in a variety of diseases, including cancer, birth defects, and other diseases. Here we reviewed recent studies on main molecules involved in the SHH signaling pathway, specifically focused on their function in epithelial tissue and appendages development, including epidermis, touch dome, hair, sebaceous gland, mammary gland, tooth, nail, gastric epithelium, and intestinal epithelium. The advance in understanding the SHH signaling pathway will give us more clues to the mechanisms of tissue repair and regeneration, as well as the development of new treatment for diseases related to dysregulation of SHH signaling pathway.

Abstract WMP36: The Sonic Hedgehog Signaling Pathway Mediates Cerebrolysin-Improved Neurological Functions after Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Zheng Gang Zhang
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Functional Recovery ◽  
Hedgehog Signaling ◽  
Artery Occlusion ◽  
Vehicle Group ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Stroke Treatment ◽  
Shh Pathway

Cerebrolysin, a mixture of neurotrophic peptides, enhances neurogenesis in experimental neurodegenerative diseases and stroke. Sonic hedgehog (Shh) signaling pathway stimulates neurogenesis after stroke. In the present study, we tested the hypothesis that the Shh signaling pathway mediates Cerebrolysin enhanced neurogenesis and functional recovery after stroke. Rats were subjected to embolic middle cerebral artery occlusion (MCAo). To examine whether blockage of the Shh signaling pathway abolishes the Cerebrolysin induced neurogenesis and functional recovery, Cyclopamine (0.2mg/kg), a Shh receptor inhbitor, or vehicle (45% 2-hydroxypropyl-cyclodextrin) was intraventricularly infused using an osmotic pump for 28 days starting 24h after MCAo with or without intraperitoneally (IP) administration of Cerebrolysin (2.5ml/kg, daily for 28d). For mitotic labeling, Bromodeoxyuridine (BrdU, 100mg/kg, IP) was administered daily for 7 days starting 24h after MCAo. Neurological functional tests including, adhesive removal test, foot-fault test, and modified neurological severity score (mNSS) were performed weekly for 5 weeks after stroke. Treatment with Cerebrolysin significantly (p<0.05) increased the number of BrdU positive cells (148±24/mm 2 vs 90±9/mm 2 in the vehicle group, n=10/group) in the ipsilateral subventricular zone (SVZ), which was associated with significant improvement of functional recovery from week 3 thought week 5 after MCAo compared with vehicle treated rats. However, inhibition of the Shh pathway with Cyclopamine significantly reduced BrdU positive cells (51±10/mm 2 ) in the SVZ, and cyclopamine treated animals failed to improve neurological function compared with vehicle treated rats. Furthermore, Cyclopamine completely reversed the effects of Cerebrolysin on SVZ cell proliferation (90±10/mm 2 ) and functional recovery. These results demonstrate that the Shh pathway mediates Cerebrolysin-enhanced neural progenitor proliferation and improves functional recovery in rats after stroke.

scholarly journals Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine

2018 ◽  
Vol 19 (10) ◽  
pp. 3040 ◽  
Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara
Keyword(s):  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Cell Biology ◽  
Hedgehog Signaling ◽  
Signal Transmission ◽  
Vascular Medicine ◽  
Endothelial Progenitor ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling

The Hedgehog (HH) signaling pathway plays an important role in embryonic and postnatal vascular development and in maintaining the homeostasis of organs. Under physiological conditions, Sonic Hedgehog (SHH), a secreted protein belonging to the HH family, regulates endothelial cell growth, promotes cell migration and stimulates the formation of new blood vessels. The present review highlights recent advances made in the field of SHH signaling in endothelial progenitor cells (EPCs). The canonical and non-canonical SHH signaling pathways in EPCs and endothelial cells (ECs) related to homeostasis, SHH signal transmission by extracellular vesicles (EVs) or exosomes containing single-strand non-coding miRNAs and impaired SHH signaling in cardiovascular diseases are discussed. As a promising therapeutic tool, the possibility of using the SHH signaling pathway for the activation of EPCs in patients suffering from cardiovascular diseases is further explored.

scholarly journals Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments

2020 ◽  
Vol 21 (3) ◽  
pp. 758 ◽  
Author(s):  
Kuo-Shyang Jeng ◽  
Chiung-Fang Chang ◽  
Shu-Sheng Lin
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Cancer Progression ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Tumor Development ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Tumor Microenvironments

During mammalian embryonic development, primary cilia transduce and regulate several signaling pathways. Among the various pathways, Sonic hedgehog (SHH) is one of the most significant. SHH signaling remains quiescent in adult mammalian tissues. However, in multiple adult tissues, it becomes active during differentiation, proliferation, and maintenance. Moreover, aberrant activation of SHH signaling occurs in cancers of the skin, brain, liver, gallbladder, pancreas, stomach, colon, breast, lung, prostate, and hematological malignancies. Recent studies have shown that the tumor microenvironment or stroma could affect tumor development and metastasis. One hypothesis has been proposed, claiming that the pancreatic epithelia secretes SHH that is essential in establishing and regulating the pancreatic tumor microenvironment in promoting cancer progression. The SHH signaling pathway is also activated in the cancer stem cells (CSC) of several neoplasms. The self-renewal of CSC is regulated by the SHH/Smoothened receptor (SMO)/Glioma-associated oncogene homolog I (GLI) signaling pathway. Combined use of SHH signaling inhibitors and chemotherapy/radiation therapy/immunotherapy is therefore key in targeting CSCs.

scholarly journals Sonic hedgehog signaling in astrocytes

2020 ◽  
Author(s):  
Steven A. Hill ◽  
Marissa Fu ◽  
A. Denise R. Garcia
Keyword(s):  
Nervous System ◽  
Signaling Pathway ◽  
Functional Properties ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Synapse Formation ◽  
Synaptic Activity ◽  
Molecular Signaling ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling

Abstract Astrocytes are complex cells that perform a broad array of essential functions in the healthy and injured nervous system. The recognition that these cells are integral components of various processes, including synapse formation, modulation of synaptic activity, and response to injury, underscores the need to identify the molecular signaling programs orchestrating these diverse functional properties. Emerging studies have identified the Sonic hedgehog (Shh) signaling pathway as an essential regulator of the molecular identity and functional properties of astrocytes. Well established as a powerful regulator of diverse neurodevelopmental processes in the embryonic nervous system, its functional significance in astrocytes is only beginning to be revealed. Notably, Shh signaling is active only in discrete subpopulations of astrocytes distributed throughout the brain, a feature that has potential to yield novel insights into functional specialization of astrocytes. Here, we discuss Shh signaling and emerging data that point to essential roles for this pleiotropic signaling pathway in regulating various functional properties of astrocytes in the healthy and injured brain.

scholarly journals Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis

2021 ◽  
Author(s):  
Xiaodong Li ◽  
Patrick J Gordon ◽  
John A Gaynes ◽  
Alexandra W Fuller ◽  
Randy Ringuette ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Downstream Targets ◽  
Shh Pathway ◽  
Pathway Activation ◽  
Retinal Neurogenesis

An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation.

scholarly journals Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine

2018 ◽  
Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara
Keyword(s):  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Cell Biology ◽  
Hedgehog Signaling ◽  
Signal Transmission ◽  
Vascular Medicine ◽  
Endothelial Progenitor ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling

The Hedgehog (Hh) signaling pathway plays an important role in embryonic and postnatal vascular development and in maintaining the homeostasis of organs. Under physiological conditions, Sonic Hedgehog (Shh), a secreted protein belonging to the Hh family, regulates endothelial cell growth, promotes cell migration, and stimulates the formation of new blood vessels. The present review highlights recent advances made in the field of Shh signaling in endothelial progenitor cells (EPCs). The canonical and non-canonical Shh signaling pathways in EPCs and endothelial cells (ECs) related to homeostasis, Shh signal transmission by extracellular vesicles (EVs) or exosomes containing single-strand non-coding miRNAs, and impaired Shh signaling in cardiovascular diseases are discussed. As a promising therapeutic tool, the possibility of using the Shh signaling pathway for the activation of EPCs in patients suffering from cardiovascular diseases is further explored.

scholarly journals Sonic Hedgehog signaling impairs ionizing radiation–induced checkpoint activation and induces genomic instability

2008 ◽  
Vol 183 (3) ◽  
pp. 385-391 ◽  
Author(s):  
Jennifer M. Leonard ◽  
Hong Ye ◽  
Cynthia Wetmore ◽  
Larry M. Karnitz
Keyword(s):  
Ionizing Radiation ◽  
Signaling Pathway ◽  
Genomic Instability ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Adaptor Protein ◽  
Sonic Hedgehog Signaling ◽  
Checkpoint Signaling ◽  
Downstream Target ◽  
Shh Pathway

The Sonic Hedgehog (Shh) pathway plays important roles in embryogenesis, stem cell maintenance, tissue repair, and tumorigenesis. Haploinsufficiency of Patched-1, a gene that encodes a repressor of the Shh pathway, dysregulates the Shh pathway and increases genomic instability and the development of spontaneous and ionizing radiation (IR)–induced tumors by an unknown mechanism. Here we show that Ptc1+/− mice have a defect in the IR-induced activation of the ATR–Chk1 checkpoint signaling pathway. Likewise, transient expression of Gli1, a downstream target of Shh signaling, disrupts Chk1 activation in human cells by preventing the interaction of Chk1 with Claspin, a Chk1 adaptor protein that is required for Chk1 activation. These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis.

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