Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity

Author(s):  
Dong-Hoon Won ◽  
Da-Bin Hwang ◽  
Yoo-Sub Shin ◽  
Shin-Young Kim ◽  
Changuk Kim ◽  
...  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarina Harshuk-Shabso ◽  
Hila Dressler ◽  
Christof Niehrs ◽  
Emil Aamar ◽  
David Enshell-Seijffers

Abstract Tissue growth in the adult is an orchestrated process that often requires biological clocks to time stem cell and progenitor activity. Here, we employed the hair follicle, which cycles between growth and regression in a timely-restricted mode, to show that some components of the hair cycle clock reside within the mesenchymal niche of the hair follicle, the dermal papilla (DP), and both Fgf and Wnt signaling pathways interact within the DP to regulate the expression of these components that include Wnt agonists (Rspondins) and antagonists (Dkk2 and Notum). The levels of Wnt agonists and antagonists in the DP are progressively reduced and elevated during the growth phase, respectively. Consequently, Wnt signaling activity in the overlying epithelial progenitor cells decreases, resulting in the induction of the regression phase. Remarkably, DP properties allow Wnt activity in the DP to persist despite the Wnt-inhibiting milieu and consequently synchronize the induction and progression of the regression phase. This study provides insight into the importance of signaling crosstalk in coupling progenitors and their niche to regulate tissue growth.


2018 ◽  
Vol 24 (1) ◽  
pp. 17-38 ◽  
Author(s):  
Sabreen F. Fostok ◽  
Mirvat El-Sibai ◽  
Marwan El-Sabban ◽  
Rabih S. Talhouk

2020 ◽  
Vol 331 ◽  
pp. 20
Author(s):  
Sarah Y.T. Robertson ◽  
Hua Mei ◽  
Chi Zhang ◽  
Jie J. Zheng ◽  
Sophie X. Deng

Author(s):  
Svitlana Melnik ◽  
Nina Hofmann ◽  
Jessica Gabler ◽  
Nicole Hecht ◽  
Wiltrud Richter

Mechanisms of WNT and bone morphogenetic protein (BMP) signaling crosstalk is in the focus of multiple biological studies, and it also has been discovered to play important roles in human mesenchymal stromal cells (MSC) that are of great interest for neocartilage engineering due to their high chondrogenic differentiation potential. However, MSC-derived chondrocytes undergo hypertrophic degeneration that impedes their clinical application for cartilage regeneration. In our previous study, we established that several microRNAs (miRs) are differentially expressed between articular chondrocytes (AC) – and MSC-derived neocartilage, with miR-181a being the most prominent candidate as key microRNA involved in the regulation of a balance between chondral and endochondral differentiation. The aim of this study was the identification of precise mRNA targets and signaling pathways regulated by miR-181a in MSC during chondrogenesis. MiR-181a was upregulated during chondrogenesis of MSC, along with an increase of the hypertrophic phenotype in resulting cartilaginous tissue. By in silico analysis combined with miR reporter assay, the WNT signaling activator and BMP signaling repressor RSPO2 was suggested as a target of miR-181a. Further validation experiments confirmed that miR-181a targets RSPO2 mRNA in MSC. It was found that in human MSC miR-181a activated BMP signaling manifested by the accumulation of SOX9 protein and increased phosphorylation of SMAD1/5/9. These effects, together with the concomitant reduction of canonical WNT signaling induced by miR-181a mimic, were in accordance with the effects expected by the loss of RSPO2, thus indicating the causative link between miR-181a and RSPO2. Moreover, we observed that a tight correlation between miR-181a and miR-218 expression levels in healthy human cartilage tissue was disrupted in osteoarthritis (OA) highlighting the importance of the WNT-BMP signaling crosstalk for preventing OA.


Author(s):  
J.S. Ryerse

Gap junctions are intercellular junctions found in both vertebrates and invertebrates through which ions and small molecules can pass. Their distribution in tissues could be of critical importance for ionic coupling or metabolic cooperation between cells or for regulating the intracellular movement of growth control and pattern formation factors. Studies of the distribution of gap junctions in mutants which develop abnormally may shed light upon their role in normal development. I report here the distribution of gap junctions in the wing pouch of 3 Drosophila wing disc mutants, vg (vestigial) a cell death mutant, 1(2)gd (lethal giant disc) a pattern abnormality mutant and 1(2)gl (lethal giant larva) a neoplastic mutant and compare these with wildtype wing discs.The wing pouch (the anlagen of the adult wing blade) of a wild-type wing disc is shown in Fig. 1 and consists of columnar cells (Fig. 5) joined by gap junctions (Fig. 6). 14000x EMs of conventionally processed, UA en bloc stained, longitudinally sectioned wing pouches were enlarged to 45000x with a projector and tracings were made on which the lateral plasma membrane (LPM) and gap junctions were marked.


Author(s):  
J. Metz ◽  
M. Merlo ◽  
W. G. Forssmann

Structure and function of intercellular junctions were studied under the electronmicroscope using conventional thin sectioning and freeze-etch replicas. Alterations of tight and gap junctions were analyzed 1. of exocrine pancreatic cells under cell isolation conditions and pancreatic duct ligation and 2. of hepatocytes during extrahepatic cholestasis.During the different steps of cell isolation of exocrine pancreatic cells, gradual changes of tight and gap junctions were observed. Tight junctions, which formed belt-like structures around the apex of control acinar cells in situ, subsequently diminished, became interrupted and were concentrated into macular areas (Fig. 1). Aggregations of membrane associated particles, which looked similar to gap junctions, were intermixed within tight junctional areas (Fig. 1). These structures continously disappeared in the last stages of the isolation procedure. The intercellular junctions were finally separated without destroying the integrity of the cell membrane, which was confirmed with porcion yellow, lanthanum chloride and horse radish peroxidase.


Author(s):  
Camillo Peracchia ◽  
Stephen J. Girsch

The fiber cells of eye lens communicate directly with each other by exchanging ions, dyes and metabolites. In most tissues this type of communication (cell coupling) is mediated by gap junctions. In the lens, the fiber cells are extensively interconnected by junctions. However, lens junctions, although morphologically similar to gap junctions, differ from them in a number of structural, biochemical and immunological features. Like gap junctions, lens junctions are regions of close cell-to-cell apposition. Unlike gap junctions, however, the extracellular gap is apparently absent in lens junctions, such that their thickness is approximately 2 nm smaller than that of typical gap junctions (Fig. 1,c). In freeze-fracture replicas, the particles of control lens junctions are more loosely packed than those of typical gap junctions (Fig. 1,a) and crystallize, when exposed to uncoupling agents such as Ca++, or H+, into pseudo-hexagonal, rhombic (Fig. 1,b) and orthogonal arrays with a particle-to-particle spacing of 6.5 nm. Because of these differences, questions have been raised about the interpretation of the lens junctions as communicating junctions, in spite of the fact that they are the only junctions interlinking lens fiber cells.


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