scholarly journals Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance

2019 ◽  
Vol 20 (12) ◽  
pp. 3076 ◽  
Author(s):  
Candice Chapouly ◽  
Sarah Guimbal ◽  
Pierre-Louis Hollier ◽  
Marie-Ange Renault

The role of Hedgehog (Hh) signaling in vascular biology has first been highlighted in embryos by Pepicelli et al. in 1998 and Rowitch et al. in 1999. Since then, the proangiogenic role of the Hh ligands has been confirmed in adults, especially under pathologic conditions. More recently, the Hh signaling has been proposed to improve vascular integrity especially at the blood–brain barrier (BBB). However, molecular and cellular mechanisms underlying the role of the Hh signaling in vascular biology remain poorly understood and conflicting results have been reported. As a matter of fact, in several settings, it is currently not clear whether Hh ligands promote vessel integrity and quiescence or destabilize vessels to promote angiogenesis. The present review relates the current knowledge regarding the role of the Hh signaling in vasculature development, maturation and maintenance, discusses the underlying proposed mechanisms and highlights controversial data which may serve as a guideline for future research. Most importantly, fully understanding such mechanisms is critical for the development of safe and efficient therapies to target the Hh signaling in both cancer and cardiovascular/cerebrovascular diseases.

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shiqin Li ◽  
Meng Wang ◽  
Yanghui Chen ◽  
Wei Wang ◽  
Junying Wu ◽  
...  

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.


2021 ◽  
Vol 22 (3) ◽  
pp. 1025
Author(s):  
Natalie Geyer ◽  
Marco Gerling

Hedgehog (Hh) signaling regulates intestinal development and homeostasis. The role of Hh signaling in cancer has been studied for many years; however, its role in colorectal cancer (CRC) remains controversial. It has become increasingly clear that the “canonical” Hh pathway, in which ligand binding to the receptor PTCH1 initiates a signaling cascade that culminates in the activation of the GLI transcription factors, is mainly organized in a paracrine manner, both in the healthy colon and in CRC. Such canonical Hh signals largely act as tumor suppressors. In addition, stromal Hh signaling has complex immunomodulatory effects in the intestine with a potential impact on carcinogenesis. In contrast, non-canonical Hh activation may have tumor-promoting roles in a subset of CRC tumor cells. In this review, we attempt to summarize the current knowledge of the Hh pathway in CRC, with a focus on the tumor-suppressive role of canonical Hh signaling in the stroma. Despite discouraging results from clinical trials using Hh inhibitors in CRC and other solid cancers, we argue that a more granular understanding of Hh signaling might allow the exploitation of this key morphogenic pathway for cancer therapy in the future.


Author(s):  
Yoshinori Abe ◽  
Nobuyuki Tanaka

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maja Dorota Wojciechowska

Purpose The purpose of the paper is to present the latest scholarly trends in the field of social capital in libraries, to review research concepts published by LIS professionals and to suggest further research possibilities in this area. Design/methodology/approach This paper presents a review and critical analysis of literature associated with research on social capital in libraries to highlight its importance for the development of LIS and its impact on the functioning of environments linked with various types of libraries. The goal of literature analysis was to determine the current condition of research on social capital in libraries. The main trends were identified and the need for further qualitative analyses, which are missing at the moment, was confirmed. Findings It was determined that, so far, LIS professionals have focussed mainly on the role of municipal libraries in developing social capital, the problem of building trust, especially in immigrant circles and the impact of libraries on promoting a civil society. Academic libraries, rural libraries, organisational capital in libraries and individual social capital of librarians were a much less frequent subject of research. The role of libraries in developing social capital in educational (primary and secondary education) and professional (non-university professionals) circles is practically non-existent in research, and it will require in-depth studies and analyses in the coming years. Originality/value This paper constitutes a synthetic review of the latest research concepts concerning social capital in libraries. It identifies the most important research trends and areas that so far have not been explored and suggests research methods to help LIS professionals design future research in this area more effectively.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Manita Kusi ◽  
Fuqiang Zhao ◽  
Dinesh Sukamani

PurposeThe study aims to scrutinize the concomitant associations between corporate social responsibility (CSR), perceived organizational support (POS), green transformational leadership (GTL) and organizational performance (OP). This paper aims to explore the role of intervening variable to measure the strength on the relationship between CSR and OP.Design/methodology/approachThis research administered a survey through self-administered questionnaire among the staff-level employees of construction companies of Nepal. Fully filled 305 responses from the participants were analyzed using a structural equation model. The study used self-structured questionnaire as research tool and face-to-face meetings as data collection technique.FindingsThe research indicates that POS showed competitive partial mediation relation between CSR and OP. Besides, a novel exploration of the moderation effect of GTL displays a supportive role in harmonizing the CSR with organizational support to achieve better OP. This study enriches empirical evidence to understand the linkage between CSR and POS in staff-level employees in the construction area. Moreover, the research shed a light on GTL 's moderating influence on the mediated model of CSR, POS and OP.Research limitations/implicationsAlthough the results of the study add to the current knowledge base, several limitations highlight avenues for future research. Future studies can explore the relationship in other study areas with added evidence on a similar result with different analysis patterns and study sample. The research model studied in the context of Nepal creating evidence as a representation for the developing countries.Originality/valueThe intervening role of POS and GTL gives new insight for the research-based organization based social behavior and performance


ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Fangfang Jin ◽  
Zhigang Guo

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.


Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F1-F17
Author(s):  
Rocío Martínez-Aguilar ◽  
Lucy E Kershaw ◽  
Jane J Reavey ◽  
Hilary O D Critchley ◽  
Jacqueline A Maybin

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.


2018 ◽  
Vol 44 (08) ◽  
pp. 765-779 ◽  
Author(s):  
Sigrid Brækkan ◽  
John-Bjarne Hansen ◽  
Line Evensen

AbstractVenous thromboembolism (VTE) is a complex multifactorial disease that represents a growing public health concern. Identification of modifiable risk factors at the population level may provide a measure to reduce the burden of VTE. In this review, we summarize current knowledge of the role of physical activity on the risk of VTE and VTE-related complications. We also discuss methodological challenges related to research on physical activity, and put forward plausible mechanisms for an association between physical activity and VTE. Up to now, published studies have reported diverging results on the relationship between physical activity and VTE, and a complex picture has emerged. However, the available evidence appears to be balanced toward a small beneficial effect of physical activity on the risk of incident VTE, but not in a dose-dependent manner. Still, the lack of an operational definition and standardized assessment method for physical activity, as well as several sources of bias, impairs the interpretation of the available literature. Additional work is necessary to understand the role and how to apply physical activity in the VTE setting. Future research should utilize objective assessment strategies of physical activity and physical fitness, account for the fluctuating nature in habitual activity levels, and explore the role of physical activity in the areas of secondary prevention and VTE-related complications.


Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1203-1212 ◽  
Author(s):  
Katerina Nestoras ◽  
Helena Lee ◽  
Jym Mohler

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.


2020 ◽  
Vol 21 (7) ◽  
pp. 2602 ◽  
Author(s):  
Vânia M. Morelli ◽  
Sigrid K. Brækkan ◽  
John-Bjarne Hansen

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.


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