scholarly journals JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

2020 ◽  
Vol 21 (3) ◽  
pp. 1015 ◽  
Author(s):  
Georgia Nikoloudaki ◽  
Sarah Brooks ◽  
Alexander P. Peidl ◽  
Dylan Tinney ◽  
Douglas W. Hamilton

In healthy individuals, the healing of soft tissues such as skin after pathological insult or post injury follows a relatively predictable and defined series of cell and molecular processes to restore tissue architecture and function(s). Healing progresses through the phases of hemostasis, inflammation, proliferation, remodeling, and concomitant with re-epithelialization restores barrier function. Soft tissue healing is achieved through the spatiotemporal interplay of multiple different cell types including neutrophils, monocytes/macrophages, fibroblasts, endothelial cells/pericytes, and keratinocytes. Expressed in most cell types, c-Jun N-terminal kinases (JNK) are signaling molecules associated with the regulation of several cellular processes involved in soft tissue wound healing and in response to cellular stress. A member of the mitogen-activated protein kinase family (MAPK), JNKs have been implicated in the regulation of inflammatory cell phenotype, as well as fibroblast, stem/progenitor cell, and epithelial cell biology. In this review, we discuss our understanding of JNKs in the regulation of cell behaviors related to tissue injury, pathology, and wound healing of soft tissues. Using models as diverse as Drosophila, mice, rats, as well as human tissues, research is now defining important, but sometimes conflicting roles for JNKs in the regulation of multiple molecular processes in multiple different cell types central to wound healing processes. In this review, we focus specifically on the role of JNKs in the regulation of cell behavior in the healing of skin, cornea, tendon, gingiva, and dental pulp tissues. We conclude that while parallels can be drawn between some JNK activities and the control of cell behavior in healing, the roles of JNK can also be very specific modes of action depending on the tissue and the phase of healing.

2001 ◽  
Vol 114 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Martin D. Bootman ◽  
Peter Lipp ◽  
Michael J. Berridge

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling ‘toolkit’, which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells.


2010 ◽  
Vol 22 (1) ◽  
Author(s):  
Weko Adhiarto ◽  
Sunardhi Mangundjaja ◽  
Makmuri Yusuf ◽  
Bambang Pontjo

The wound healing process of the soft tissue aims to accelerate the closing of the wound by recurring, restoring the function, and minimizing the scar tissue. This process has to occur in the surgery process to obtain better-wound healing. The aim of this study was to know the stimulation effect of the wound dressing to accelerate the wound healing process of the soft tissue using Collagen (amino acid) and Amnion (proteinase inhibitors). This true experimental study was done to 36 mice (Sprague Dawley) that were divided into three different groups, two groups were the treatment groups and one group was the control group. Each group was adapted in Pathology Laboratory of Faculty of Veterinary Medicine Bogor Agricultural University. All of the mice were injured on the skin by incising the right side of the back for 2 cm in length and 4 mm in depth and then cleaned with 0.9% NaCl solution. To the first group of treatment, the wound was applicated by Amnion, and the second group was applicated by Collagen. Each 4 mice of all group were a termination by ether and encryption on the wounded tissue was conducted on day 3rd, 7th, and 14th. Assessment for a number of fibroblast and collagen synthesis on the wound of back tissue was conducted with the histological examination by painted using hematoxylin-eosin. The results concluded that Collagen application was influencing the mean of fibroblast higher than Amnion, and the lowest was controlled with statistically significant. The mean of collagen used Collagen lower than Amnion, and the lowest was control with statistically significant. It could be concluded that collagen application was preeminent in increasing the productivity of the fibroblast, as well as in developing forms of the collagen synthesis compared with Amnion and control.


2021 ◽  
Author(s):  
Jean A. Castillo-Badillo ◽  
N. Gautam

Cell shape regulation is important but the mechanisms that govern shape are not fully understood, in part due to limited experimental models where cell shape changes and underlying molecular processes can be rapidly and non-invasively monitored in real time. Here, we use an optogenetic tool to activate RhoA in the middle of mononucleated macrophages to induce contraction, resulting in a side with the nucleus that retains its shape and a non-nucleated side which was unable to maintain its shape and collapsed. In cells overexpressing focal adhesion kinase (FAK), the non-nucleated side exhibited a wide flat morphology and was similar in adhesion area to the nucleated side. In cells overexpressing fascin, an actin bundling protein, the non-nucleated side assumed a spherical shape and was similar in height to the nucleated side. This effect of fascin was also observed in fibroblasts even without inducing furrow formation. Based on these results, we conclude that FAK and fascin work together to maintain cell shape by regulating adhesion area and height, respectively, in different cell types.


Author(s):  
Thibaut Brunet ◽  
Marvin Albert ◽  
William Roman ◽  
Danielle C. Spitzer ◽  
Nicole King

The evolution of different cell types was a key process of early animal evolution1–3. Two fundamental cell types, epithelial cells and amoeboid cells, are broadly distributed across the animal tree of life4,5 but their origin and early evolution are unclear. Epithelial cells are polarized, have a fixed shape and often bear an apical cilium and microvilli. These features are shared with choanoflagellates – the closest living relatives of animals – and are thought to have been inherited from their last common ancestor with animals1,6,7. The deformable amoeboid cells of animals, on the other hand, seem strikingly different from choanoflagellates and instead evoke more distantly related eukaryotes, such as diverse amoebae – but it has been unclear whether that similarity reflects common ancestry or convergence8. Here, we show that choanoflagellates subjected to spatial confinement differentiate into an amoeboid phenotype by retracting their flagella and microvilli, generating blebs, and activating myosin-based motility. Choanoflagellate cell crawling is polarized by geometrical features of the substrate and allows escape from confined microenvironments. The confinement-induced amoeboid switch is conserved across diverse choanoflagellate species and greatly expands the known phenotypic repertoire of choanoflagellates. The broad phylogenetic distribution of the amoeboid cell phenotype across animals9–14 and choanoflagellates, as well as the conserved role of myosin, suggests that myosin-mediated amoeboid motility was present in the life history of their last common ancestor. Thus, the duality between animal epithelial and crawling cells might have evolved from a temporal phenotypic switch between flagellate and amoeboid forms in their single-celled ancestors3,15,16.


2013 ◽  
Vol 7 (1) ◽  
pp. 614-618 ◽  
Author(s):  
Chad G. Williams ◽  
Michael J. Coffey ◽  
Peter Shorten ◽  
James D. Lyions ◽  
Richard T. Laughlin

Background: With high energy fractures to the calcaneus there is the potential for significant bone loss. The loss of bone can make it difficult to fully regain calcaneal alignment. In addition these fractures are often associated with significant soft tissue injury. These two factors make it difficult to address this injury in a single stage, and can have significant complications. To address these issues our initial goal in treatment has been restoration of calcaneal alignment and stabilization of the surrounding soft tissue, followed by delayed/staged subtalar arthrodesis. Methods: Patients with calcaneus fractures treated by a single surgeon from 2002 to 2012 were reviewed. Injuries which were found to have medial extrusion of the posterior facet and bone loss, and subsequently underwent a staged protocol involving early provisional fixation and late subtalar fusion were included. Results: We treated 6 calcaneus fractures with bone loss. All patients were treated with staged subtalar fusion after initial irrigation and debridement and provisional fixation. No soft-tissue complications were noted after the fusion procedure in any of the six cases. Fusion occurred in all six patients at an average of 20.6 weeks (range, 13-23 weeks). All patients were able to ambulate and wear a regular shoe by one year following the initial injury. Conclusion: It is important in the high energy calcaneus fracture to assess for both soft tissue integrity and bone loss. A thorough debridement of both the soft tissues and any devitalized bone should be performed as well as provisional fixation which attempts to restore near normal calcaneal anatomy. Definitive fusion should not be performed until the soft tissues have fully recovered.


2014 ◽  
pp. 173-178 ◽  
Author(s):  
Carlos Oliver Valderrama-Molina ◽  
Mauricio Estrada-Castrillón ◽  
Jorge Andres Hincapie ◽  
Luz Helena Lugo-Agudelo

Background: The soft tissues injury in periarticular fractures of the lower extremities determines the proper time to perform bone fixation. Objetive: The aim of this study was to determine the intra and interobserver agreement in the Tscherne classification. Methods: This is a descriptive, prospective study for patients admitted to the Pablo Tobón Uribe Hospital (PTUH) with tibial plateau or tibial pilon fractures. We performed a standardize evaluation using video photography at the time of admission and 24, 48, and 72 h after admission. Fifteen five reviewers who had various levels of training produced a total of 1,200 observations. The intra- and interobserver agreement was assessed using a weighted kappa for multiple raters and more than two categories. Results: Twenty patients were admitted with tibial plateau and tibial pilon fractures. The intraobserver agreement for all 15 raters was kappa 0.81 (95% CI 0.79-0.83), and the interobserver agreement for all 15 raters was kappa 0.65 (95% CI 0.55-0.73). The interobserver agreement at 24 h was kappa 0.67 (95% CI 0.46-0.86). Conclusions:Classifying the severity of soft tissue injury is critical in planning the surgical management of fractures of the lower extremities. Based on our results, we can reasonably argue that the Tscherne classification produced an adequate level of agreement and could be used to standardize and to guide the treatment, and to conduct research studies. Level of Evidence: Level IV, Case Series


PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Eimear M. Mullen ◽  
Peili Gu ◽  
Austin J. Cooney

Embryonic stem (ES) cells have great therapeutic potential because they are capable of indefinite self-renewal and have the potential to differentiate into over 200 different cell types that compose the human body. The switch from the pluripotent phenotype to a differentiated cell involves many complex signaling pathways including those involving LIF/Stat3 and the transcription factors Sox2, Nanog and Oct-4. Many nuclear receptors play an important role in the maintenance of pluripotence (ERRβ, SF-1, LRH-1, DAX-1) repression of the ES cell phenotype (RAR, RXR, GCNF) and also the differentiation of ES cells (PPARγ). Here we review the roles of the nuclear receptors involved in regulating these important processes in ES cells.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 484
Author(s):  
Maria Patrizia Mongiardi ◽  
Manuela Pellegrini ◽  
Roberto Pallini ◽  
Andrea Levi ◽  
Maria Laura Falchetti

Cellular senescence participates to fundamental processes like tissue remodeling in embryo development, wound healing and inhibition of preneoplastic cell growth. Most senescent cells display common hallmarks, among which the most characteristic is a permanent (or long lasting) arrest of cell division. However, upon senescence, different cell types acquire distinct phenotypes, which also depend on the specific inducing stimuli. Senescent cells are metabolically active and secrete a collection of growth factors, cytokines, proteases, and matrix-remodeling proteins collectively defined as senescence-associated secretory phenotype, SASP. Through SASP, senescent cells modify their microenvironment and engage in a dynamic dialog with neighbor cells. Senescence of neoplastic cells, at least temporarily, reduces tumor expansion, but SASP of senescent cancer cells as well as SASP of senescent stromal cells in the tumor microenvironment may promote the growth of more aggressive cancer subclones. Here, we will review recent data on the mechanisms and the consequences of cancer-therapy induced senescence, enlightening the potentiality and the risk of senescence inducing treatments.


Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 110 ◽  
Author(s):  
Carlos de la Calle-Fabregat ◽  
Octavio Morante-Palacios ◽  
Esteban Ballestar

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.


2000 ◽  
Vol 278 (2) ◽  
pp. F192-F201 ◽  
Author(s):  
Dennis Brown

Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney.


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