scholarly journals Fibroblast Memory in Development, Homeostasis and Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2840
Author(s):  
Thomas Kirk ◽  
Abubkr Ahmed ◽  
Emanuel Rognoni
Keyword(s):  
Cell Population ◽  
Structural Integrity ◽  
Tissue Homeostasis ◽  
Metabolic Memory ◽  
Anatomical Location ◽  
Environmental Stimulus ◽  
Environmental Stimuli ◽  
Biological Memory ◽  
Underlying Mechanisms ◽  
And Function

Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus. While it is well established that fibroblasts retain a memory of their anatomical location, how other environmental stimuli influence fibroblast behaviour and function is less clear. The ability of fibroblasts to respond and memorise different environmental stimuli is essential for tissue development and homeostasis and may become dysregulated in chronic disease conditions such as fibrosis and cancer. Here we summarise the four emerging key areas of fibroblast adaptation: positional, mechanical, inflammatory, and metabolic memory and highlight the underlying mechanisms and their implications in tissue homeostasis and disease.

scholarly journals Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 336
Author(s):  
Roberta Melchionna ◽  
Paola Trono ◽  
Annalisa Tocci ◽  
Paola Nisticò
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Actin Dynamics ◽  
Human Tissues ◽  
Cellular Functions ◽  
Tgfβ Signaling ◽  
Physical Mechanisms ◽  
And Function

Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

scholarly journals Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luís Crisóstomo ◽  
Ivana Jarak ◽  
Luís P. Rato ◽  
João F. Raposo ◽  
Rachel L. Batterham ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Feeding Habits ◽  
Reproductive Function ◽  
Principal Component ◽  
Testicular Tissue ◽  
Sperm Parameters ◽  
Metabolic Memory ◽  
High Fat ◽  
And Function ◽  
The Impact

AbstractThe consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational “inherited metabolic memory” in the testicular tissue, characterized by changes in testicular metabolome and function.

scholarly journals Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Hsiang-Hao Chuang ◽  
Yen-Yi Zhen ◽  
Yu-Chen Tsai ◽  
Cheng-Hao Chuang ◽  
Ming-Shyan Huang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Suppressors ◽  
Protein Conformation ◽  
Genome Stability ◽  
Recent Progress ◽  
Multiple Roles ◽  
Cancer Development ◽  
Cancer Hallmarks ◽  
Underlying Mechanisms ◽  
And Function

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-chi Shen ◽  
Adrienne Niederriter Shami ◽  
Lindsay Moritz ◽  
Hailey Larose ◽  
Gabriel L. Manske ◽  
...  
Keyword(s):  
Tissue Homeostasis ◽  
Testicular Development ◽  
Myoid Cells ◽  
Regenerative Capacity ◽  
Adult Testis ◽  
Mesenchymal Progenitors ◽  
And Function ◽  
Potential Reserve ◽  
Resident Fibroblast

AbstractTesticular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21lin cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21lin cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility.

scholarly journals Clinical Relevance of Elastin in the Structure and Function of Skin

2021 ◽  
Author(s):  
Leslie Baumann ◽  
Eric F Bernstein ◽  
Anthony S Weiss ◽  
Damien Bates ◽  
Shannon Humphrey ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Relevance ◽  
Structural Integrity ◽  
Elastic Fiber ◽  
Subcutaneous Fat ◽  
Structure And Function ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Superficial Dermis ◽  
And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

scholarly journals Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Huban Thomas Rajarethnem ◽  
Kumar Megur Ramakrishna Bhat ◽  
Malsawmzuali Jc ◽  
Siva Kumar Gopalkrishnan ◽  
Ramesh Babu Mugundhu Gopalram ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Structural Integrity ◽  
Fetal Brain ◽  
Normal Pregnancy ◽  
Saline Control ◽  
Fetal Brain Development ◽  
Essential Nutrient ◽  
Combined Supplementation ◽  
And Function ◽  
The Brain

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p<0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p<0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

Antimicrobial mode of action of secretions from the metapleural gland ofMytmecia gulosa(Australian bull ant)

1995 ◽  
Vol 41 (2) ◽  
pp. 136-144 ◽  
Author(s):  
J. A. Mackintosh ◽  
J. E. Trimble ◽  
A. J. Beattie ◽  
D. A. Veal ◽  
M. K. Jones ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antimicrobial Agents ◽  
Structural Integrity ◽  
Phospholipid Bilayer ◽  
Active Components ◽  
Cytoplasmic Matrix ◽  
Metapleural Glands ◽  
Total Leakage ◽  
Membrane Bound ◽  
And Function

Secretions from exocrine metapleural glands of Myrmecia gulosa (Australian bull ant) exhibit broad-spectrum antimicrobial activity. Treatment of the yeast Candida albicans with metapleural secretion resulted in the rapid and total leakage of K+ions from cells within 10 min. Ultrastructural analysis of the bacteria Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa, and cells and protoplasts of Candida albicans demonstrated gross damage of the cell membrane and aggregation of the cytoplasmic matrix of treated cells. Degradation of membrane-bound organelles was also observed in Candida albicans. The antimicrobially active components of metapleural secretions were nonpolar and interacted with the phospholipid bilayer, causing damage to the structural integrity of liposomes and the release of carboxyfluorescein. The data suggest that the antimicrobial agents in metapleural secretion act primarily by disrupting the structure and function of the phospholipid bilayer of the cytoplasmic membrane.Key words: ant metapleural secretion, antimicrobial, Candida albicans, cytoplasmic membrane.

scholarly journals Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila

Neuron ◽  
2006 ◽  
Vol 51 (2) ◽  
pp. 275 ◽  
Author(s):  
Dhananjay A. Wagh ◽  
Tobias M. Rasse ◽  
Esther Asan ◽  
Alois Hofbauer ◽  
Isabell Schwenkert ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Active Zones ◽  
And Function

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

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