The Hedgehog Signaling Pathway in Ischemic Tissues

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

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Potential role of Hedgehog signaling pathway and myofibroblastic differentiation in central giant cell granuloma—A preliminary study

Journal of Oral Pathology and Medicine ◽

10.1111/jop.12949 ◽

2019 ◽

Vol 48 (9) ◽

pp. 855-860

Author(s):

Vinicius Rio Verde Melo Muniz ◽

Fábio Daumas Nunes ◽

Flávia Caló de Aquino Xavier ◽

Maria Cristina Teixeira Cangussu ◽

Roseana Almeida Freitas ◽

...

Keyword(s):

Giant Cell ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Potential Role ◽

Hedgehog Signaling Pathway ◽

Giant Cell Granuloma ◽

Central Giant Cell Granuloma ◽

Preliminary Study ◽

Myofibroblastic Differentiation

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Understanding the Hedgehog Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Necessary Step toward a Cure

Biology ◽

10.3390/biology10040255 ◽

2021 ◽

Vol 10 (4) ◽

pp. 255

Author(s):

Daniel Lainez-González ◽

Juana Serrano-López ◽

Juan Manuel Alonso-Domínguez

Keyword(s):

Stem Cells ◽

Acute Myeloid Leukemia ◽

Signaling Pathway ◽

Myeloid Leukemia ◽

Hedgehog Signaling ◽

Hedgehog Signaling Pathway ◽

Leukemic Stem Cells ◽

Hh Signaling ◽

Acute Myeloid

A better understanding of how signaling pathways govern cell fate is fundamental to advances in cancer development and treatment. The initialization of different tumors and their maintenance are caused by the deregulation of different signaling pathways and cancer stem cell maintenance. Quiescent stem cells are resistant to conventional chemotherapeutic treatments and, consequently, are responsible for disease relapse. In this review we focus on the conserved Hedgehog (Hh) signaling pathway which is involved in regulating the cell cycle of hematopoietic and leukemic stem cells. Thus, we examine the role of the Hh signaling pathway in normal and leukemic stem cells and dissect its role in acute myeloid leukemia. We explain not only the connection between illness and the signaling pathway but also evaluate innovative therapeutic approaches that could affect the outcome of patients with acute myeloid leukemia. We found that many aspects of the Hedgehog signaling pathway remain unknown. The role of Hh has only been proven in embryo and hematopoietic stem cell development. Further research is needed to elucidate the role of GLI transcription factors for therapeutic targeting. Glasdegib, an SMO inhibitor, has shown clinical activity in acute myeloid leukemia; however, its mechanism of action is not clear.

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The Role of Sonic Hedgehog-Gli2 Pathway in the Masculinization of External Genitalia

Endocrinology ◽

10.1210/en.2011-0263 ◽

2011 ◽

Vol 152 (7) ◽

pp. 2894-2903 ◽

Cited By ~ 42

Author(s):

Shinichi Miyagawa ◽

Daisuke Matsumaru ◽

Aki Murashima ◽

Akiko Omori ◽

Yoshihiko Satoh ◽

...

Keyword(s):

Signaling Pathway ◽

Sonic Hedgehog ◽

Hedgehog Signaling ◽

External Genitalia ◽

Sexually Dimorphic ◽

Hedgehog Signaling Pathway ◽

Initial Development ◽

Urethral Plate ◽

Male External Genitalia

During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.

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Role of knot (kn) in Wing Patterning in Drosophila

Genetics ◽

10.1093/genetics/147.3.1203 ◽

1997 ◽

Vol 147 (3) ◽

pp. 1203-1212 ◽

Cited By ~ 1

Author(s):

Katerina Nestoras ◽

Helena Lee ◽

Jym Mohler

Keyword(s):

Hedgehog Signaling ◽

Imaginal Disc ◽

Hedgehog Signaling Pathway ◽

Posterior Compartment ◽

Drosophila Wing ◽

Compartment Boundary ◽

Hh Signaling ◽

Embryonic Segmentation ◽

Anterior Posterior

We have undertaken a genetic analysis of new strong alleles of knot (kn). The original kn1 mutation causes an alteration of wing patterning similar to that associated with mutations of fused (fu), an apparent fusion of veins 3 and 4 in the wing. However, unlike fu, strong kn mutations do not affect embryonic segmentation and indicate that kn is not a component of a general Hh (Hedgehog)-signaling pathway. Instead we find that kn has a specific role in those cells of the wing imaginal disc that are subject to ptc-mediated Hh-signaling. Our results suggest a model for patterning the medial portion of the Drosophila wing, whereby the separation of veins 3 and 4 is maintained by kn activation in the intervening region in response to Hh-signaling across the adjacent anterior-posterior compartment boundary.

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Role of the Hedgehog Signaling Pathway in Regulating the Behavior of Germline Stem Cells

Stem Cells International ◽

10.1155/2017/5714608 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Shiqin Li ◽

Meng Wang ◽

Yanghui Chen ◽

Wei Wang ◽

Junying Wu ◽

...

Keyword(s):

Stem Cells ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Adult Stem Cells ◽

Reproductive Function ◽

Future Research ◽

Germline Stem Cells ◽

Proliferation And Differentiation ◽

Hh Signaling

Germline stem cells (GSCs) are adult stem cells that are responsible for the production of gametes and include spermatogonial stem cells (SSCs) and ovarian germline stem cells (OGSCs). GSCs are located in a specialized microenvironment in the gonads called the niche. Many recent studies have demonstrated that multiple signals in the niche jointly regulate the proliferation and differentiation of GSCs, which is of significance for reproductive function. Previous studies have demonstrated that the hedgehog (Hh) signaling pathway participates in the proliferation and differentiation of various stem cells, including GSCs in Drosophila and male mammals. Furthermore, the discovery of mammalian OGSCs challenged the traditional opinion that the number of primary follicles is fixed in postnatal mammals, which is of significance for the reproductive ability of female mammals and the treatment of diseases related to germ cells. Meanwhile, it still remains to be determined whether the Hh signaling pathway participates in the regulation of the behavior of OGSCs. Herein, we review the current research on the role of the Hh signaling pathway in mediating the behavior of GSCs. In addition, some suggestions for future research are proposed.

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Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

10.21203/rs.3.rs-15484/v1 ◽

2020 ◽

Author(s):

You Li ◽

Guohui Xiong ◽

Jun Tan ◽

Shudi Wang ◽

Ziyu Zhang ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Signaling Pathway ◽

Granulosa Cells ◽

Hedgehog Signaling ◽

Polycystic Ovary ◽

Hedgehog Signaling Pathway ◽

Ovary Syndrome ◽

Expression Levels ◽

Pcos Group ◽

Hh Signaling

Abstract The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

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