scholarly journals Themes in fibrosis and gastrointestinal inflammation

2011 ◽  
Vol 300 (5) ◽  
pp. G677-G683 ◽  
Author(s):  
Claudio Fiocchi ◽  
P. Kay Lund
Keyword(s):  
Wound Healing ◽  
Tissue Injury ◽  
Cell Types ◽  
Loss Of Function ◽  
Intestinal Fibrosis ◽  
Gastrointestinal Health ◽  
Molecular Approaches ◽  
Organ Systems ◽  
Culture Models ◽  
Gastrointestinal Inflammation

Wound healing is an appropriate response to inflammation and tissue injury in the gastrointestinal tract. If wound healing responses are excessive, perpetuated, or prolonged, they lead to fibrosis, distortion of tissue architecture, and loss of function. This introductory editorial and the minireviews or reviews in this themes series highlight the diversity in severity and location of fibrosis in response to gastrointestinal inflammation. The multiplicity of cellular and molecular mediators and new players, including stem cells or extracellular matrix-producing cells derived from nonmesenchymal cell types, is reviewed. Comparisons of inflammation-induced fibrosis across organ systems and the need for integrated and systems-based molecular approaches, new imaging modalities, well-characterized animal models, cell culture models, and improved diagnostic or predictive markers are reviewed. To date, intestinal fibrosis has received much less attention than inflammation in terms of defining mechanisms and underlying causes. This themes series aims to illustrate the importance of research in this area in gastrointestinal health and disease.

scholarly journals Cell type- and tissue-specific functions of ecto-5′-nucleotidase (CD73)

2019 ◽  
Vol 317 (6) ◽  
pp. C1079-C1092 ◽  
Author(s):  
Marquet Minor ◽  
Karel P. Alcedo ◽  
Rachel A. Battaglia ◽  
Natasha T. Snider
Keyword(s):  
Cortical Plasticity ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Endothelial Permeability ◽  
Cell Types ◽  
Multiple Organ ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Organ Systems

Ecto-5′-nucleotidase [cluster of differentiation 73 (CD73)] is a ubiquitously expressed glycosylphosphatidylinositol-anchored glycoprotein that converts extracellular adenosine 5′-monophosphate to adenosine. Anti-CD73 inhibitory antibodies are currently undergoing clinical testing for cancer immunotherapy. However, many protective physiological functions of CD73 need to be taken into account for new targeted therapies. This review examines CD73 functions in multiple organ systems and cell types, with a particular focus on novel findings from the last 5 years. Missense loss-of-function mutations in the CD73-encoding gene NT5E cause the rare disease “arterial calcifications due to deficiency of CD73.” Aside from direct human disease involvement, cellular and animal model studies have revealed key functions of CD73 in tissue homeostasis and pathology across multiple organ systems. In the context of the central nervous system, CD73 is antinociceptive and protects against inflammatory damage, while also contributing to age-dependent decline in cortical plasticity. CD73 preserves barrier function in multiple tissues, a role that is most evident in the respiratory system, where it inhibits endothelial permeability in an adenosine-dependent manner. CD73 has important cardioprotective functions during myocardial infarction and heart failure. Under ischemia-reperfusion injury conditions, rapid and sustained induction of CD73 confers protection in the liver and kidney. In some cases, the mechanism by which CD73 mediates tissue injury is less clear. For example, CD73 has a promoting role in liver fibrosis but is protective in lung fibrosis. Future studies that integrate CD73 regulation and function at the cellular level with physiological responses will improve its utility as a disease target.

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
Keyword(s):  
Wound Healing ◽  
Soft Tissue ◽  
Cell Biology ◽  
Soft Tissues ◽  
Tissue Injury ◽  
Cell Types ◽  
Cell Phenotype ◽  
Cell Behavior ◽  
Molecular Processes ◽  
Different Cell Types

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.

scholarly journals Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

2015 ◽  
Vol 112 (36) ◽  
pp. E5068-E5077 ◽  
Author(s):  
Nikolai Schnittke ◽  
Daniel B. Herrick ◽  
Brian Lin ◽  
Jesse Peterson ◽  
Julie H. Coleman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Olfactory Epithelium ◽  
Tissue Injury ◽  
Cell Types ◽  
Stem Cell Population ◽  
Basal Cells ◽  
Loss Of Function ◽  
Down Regulation ◽  
Horizontal Basal Cells

Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.

scholarly journals Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imran Khan ◽  
Saeed Ur Rahman ◽  
Elieza Tang ◽  
Karl Engel ◽  
Bradford Hall ◽  
...  
Keyword(s):  
Wound Healing ◽  
Surface Temperature ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Cell Types ◽  
Wound Management ◽  
Burn Wound ◽  
Burn Wound Healing ◽  
Tissue Healing ◽  
Tgf Β1

AbstractThe severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-β1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-β signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-β dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-β1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-β1/β3 knock-in (TGF-β1Lβ3/Lβ3) mice. PBM treatments failed to activate the chimeric TGF-β1Lβ3/Lβ3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-β1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.

scholarly journals Molecular Mechanisms of Neuroimmune Crosstalk in the Pathogenesis of Stroke

2021 ◽  
Vol 22 (17) ◽  
pp. 9486
Author(s):  
Yun Hwa Choi ◽  
Collin Laaker ◽  
Martin Hsu ◽  
Peter Cismaru ◽  
Matyas Sandor ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Lymphatic Vessels ◽  
Immunological Response ◽  
Cell Types ◽  
Multiple Organ ◽  
Post Stroke ◽  
Organ Systems ◽  
The Brain

Stroke disrupts the homeostatic balance within the brain and is associated with a significant accumulation of necrotic cellular debris, fluid, and peripheral immune cells in the central nervous system (CNS). Additionally, cells, antigens, and other factors exit the brain into the periphery via damaged blood–brain barrier cells, glymphatic transport mechanisms, and lymphatic vessels, which dramatically influence the systemic immune response and lead to complex neuroimmune communication. As a result, the immunological response after stroke is a highly dynamic event that involves communication between multiple organ systems and cell types, with significant consequences on not only the initial stroke tissue injury but long-term recovery in the CNS. In this review, we discuss the complex immunological and physiological interactions that occur after stroke with a focus on how the peripheral immune system and CNS communicate to regulate post-stroke brain homeostasis. First, we discuss the post-stroke immune cascade across different contexts as well as homeostatic regulation within the brain. Then, we focus on the lymphatic vessels surrounding the brain and their ability to coordinate both immune response and fluid homeostasis within the brain after stroke. Finally, we discuss how therapeutic manipulation of peripheral systems may provide new mechanisms to treat stroke injury.

scholarly journals Integrated spatial multiomics reveals fibroblast fate during tissue repair

2021 ◽  
Vol 118 (41) ◽  
pp. e2110025118
Author(s):  
Deshka S. Foster ◽  
Michael Januszyk ◽  
Kathryn E. Yost ◽  
Malini S. Chinta ◽  
Gunsagar S. Gulati ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Integrated Analysis ◽  
Skin Injury ◽  
Wound Model ◽  
Organ Systems ◽  
Proliferation And Differentiation ◽  
Transgenic Lines ◽  
Complex Organ

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.

scholarly journals Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development

2020 ◽  
Vol 7 (3) ◽  
pp. 31
Author(s):  
Lilong Guo ◽  
Janiece Glover ◽  
Alyssa Risner ◽  
Christina Wang ◽  
Diana Fulmer ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Expression Profiles ◽  
Cell Types ◽  
Careful Consideration ◽  
Loss Of Function ◽  
Valve Development ◽  
Dynamic Expression ◽  
Organ Systems ◽  
Cardiac Valve Development ◽  
Specific Regulation

β-catenin has been widely studied in many animal and organ systems across evolution, and gain or loss of function has been linked to a number of human diseases. Yet fundamental knowledge regarding its protein expression and localization remains poorly described. Thus, we sought to define whether there was a temporal and cell-specific regulation of β-catenin activities that correlate with distinct cardiac morphological events. Our findings indicate that activated nuclear β-catenin is primarily evident early in gestation. As development proceeds, nuclear β-catenin is down-regulated and becomes restricted to the membrane in a subset of cardiac progenitor cells. After birth, little β-catenin is detected in the heart. The co-expression of β-catenin with its main transcriptional co-factor, Lef1, revealed that Lef1 and β-catenin expression domains do not extensively overlap in the cardiac valves. These data indicate mutually exclusive roles for Lef1 and β-catenin in most cardiac cell types during development. Additionally, these data indicate diverse functions for β-catenin within the nucleus and membrane depending on cell type and gestational timing. Cardiovascular studies should take into careful consideration both nuclear and membrane β-catenin functions and their potential contributions to cardiac development and disease.

scholarly journals Epithelial Cell Coculture Models for Studying Infectious Diseases: Benefits and Limitations

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin L. Duell ◽  
Allan W. Cripps ◽  
Mark A. Schembri ◽  
Glen C. Ulett
Keyword(s):  
Cell Culture ◽  
Epithelial Cell ◽  
Infectious Diseases ◽  
Cell Types ◽  
Bacterial Disease ◽  
Organ Systems ◽  
Wide Range ◽  
Host Pathogen ◽  
Culture Models ◽  
Cell Culture Models

Countless in vitro cell culture models based on the use of epithelial cell types of single lineages have been characterized and have provided insight into the mechanisms of infection for various microbial pathogens. Diverse culture models based on disease-relevant mucosal epithelial cell types derived from gastrointestinal, genitourinary, and pulmonary organ systems have delineated many key host-pathogen interactions that underlie viral, parasitic, and bacterial disease pathogenesis. An alternative to single lineage epithelial cell monoculture, which offers more flexibility and can overcome some of the limitations of epithelial cell culture models based on only single cell types, is coculture of epithelial cells with other host cell types. Various coculture models have been described, which incorporate epithelial cell types in culture combination with a wide range of other cell types including neutrophils, eosinophils, monocytes, and lymphocytes. This paper will summarize current models of epithelial cell coculture and will discuss the benefits and limitations of epithelial cell coculture for studying host-pathogen dynamics in infectious diseases.

scholarly journals Integrated spatial multi-omics reveals fibroblast fate during tissue repair

2021 ◽  
Author(s):  
Deshka S Foster ◽  
Michael Januszyk ◽  
Malini S Chinta ◽  
Kathryn E Yost ◽  
Gunsagar Singh Gulati ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Fate ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Integrated Analysis ◽  
Wound Model ◽  
Organ Systems ◽  
Proliferation And Differentiation ◽  
Transgenic Lines ◽  
Complex Organ

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to define the mechanisms controlling cell fate during migration, proliferation, and differentiation following tissue injury and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

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