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

Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara

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.

2018 ◽  
Vol 19 (10) ◽  
pp. 3040 ◽  
Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara

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.


Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara

The Hedgehog (Hh) signaling pathway plays an essential role in embryonic and postnatal vasculature development and homeostasis of organs. Under physiological condition, Hh family’s member Sonic Hedgehog (SHh) regulates endothelial cell growth, promotes cell migration, and induces the construction of blood vessels. In this review, we highlight recent topics in EPC biology, regarding current advance in SHh canonical and non-canonical signaling pathway in EPCs and EC biology in terms of homeostasis, extracellular SHh signal transmission by parental cell-derived extracellular vesicle (exosomes containing single-strand non-codding miRNA), and SHh signal impairment in cardiovascular diseases. Also, we discuss SHh signaling pathway activation of EPCs as a promising therapeutic tool against cardiovascular disease patients.


2019 ◽  
Vol 7 ◽  
pp. 3
Author(s):  
Lu Zheng ◽  
Chen Rui ◽  
Hao Zhang ◽  
Jing Chen ◽  
Xiuzhi Jia ◽  
...  

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.


2020 ◽  
Vol 21 (3) ◽  
pp. 758 ◽  
Author(s):  
Kuo-Shyang Jeng ◽  
Chiung-Fang Chang ◽  
Shu-Sheng Lin

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.


Author(s):  
Steven A. Hill ◽  
Marissa Fu ◽  
A. Denise R. Garcia

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.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Zheng Gang Zhang

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.


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