How to Keep Myofibroblasts under Control: Culture of Mouse Skin Fibroblasts on Soft Substrates.

During the physiological healing of skin wounds, fibroblasts recruited from the uninjured adjacent dermis and deeper subcutaneous fascia layers are transiently activated into myofibroblasts to first secrete and then contract collagen-rich extracellular matrix into a mechanically resistant scar. Scar tissue restores skin integrity after damage but comes at the expense of poor esthetics and loss of tissue function. Stiff scar matrix also mechanically activates various precursor cells into myofibroblasts in a positive feedback loop.

Correction: Histone Demethylase JMJD2B Functions as a Co-Factor of Estrogen Receptor in Breast Cancer Proliferation and Mammary Gland Development.

[This corrects the article DOI: 10.1371/journal.pone.

Compromised dental cells viability following teeth-whitening exposure.

This study aimed to assess the viability of dental cells following time-dependent carbamide peroxide teeth-whitening treatments using an in-vitro dentin perfusion assay model. 30 teeth were exposed to 5% or 16% CP gel (4 h daily) for 2-weeks. The enamel organic content was measured with thermogravimetry.

A Rodent Model of Hypertrophic Scarring: Splinting of Rat Wounds.

Human hypertrophic scars are the result of imperfect healing of skin, which is particularly evident from the scars developing after severe burns. In contrast, mouse and rat full-thickness skin wounds heal normally without forming visible scar tissue, which reduces the suitability of rodent models for the study of skin scarring. We here provide a simple procedure to splint the edges of full-thickness rodent skin with a sutured plastic frame that prevents wound closure by granulation tissue contraction.

Myofibroblast Markers and Microscopy Detection Methods in Cell Culture and Histology.

The identification of myofibroblasts is essential for mechanistic in vitro studies, cell-based drug tests, and to assess the level of fibrosis in experimental animal or human fibrosis. The name myo-fibroblast was chosen in 1971 to express that the formation of contractile features-stress fibers is the essential criterion to define these cells. Additional neo-expression of α-smooth muscle actin (α-SMA) in stress fibers has become the most widely used molecular marker.

Kindlin-2 Mediates Mechanical Activation of Cardiac Myofibroblasts.

We identify the focal adhesion protein kindlin-2 as player in a novel mechanotransduction pathway that controls profibrotic cardiac fibroblast to myofibroblast activation. Kindlin-2 is co-upregulated with the myofibroblast marker α-smooth muscle actin (α-SMA) in fibrotic rat hearts and in human cardiac fibroblasts exposed to fibrosis-stiff culture substrates and pro-fibrotic TGF-β1. Stressing fibroblasts using ferromagnetic microbeads, stretchable silicone membranes, and cell contraction agonists all result in kindlin-2 translocation to the nucleus.

Combined use of GABA and sitagliptin promotes human β-cell proliferation and reduces apoptosis.

γ-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent β-cell survival and function. In human β-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic β-cell protective effect in mice islets.

The myofibroblast at a glance.

In 1971, Gabbiani and co-workers discovered and characterized the "" (contraction) in rat wound granulation tissue and, accordingly, named these cells 'myofibroblasts'. Now, myofibroblasts are not only recognized for their physiological role in tissue repair but also as cells that are key in promoting the development of fibrosis in all organs. In this Cell Science at a Glance and the accompanying poster, we provide an overview of the current understanding of central aspects of myofibroblast biology, such as their definition, activation from different precursors, the involved signaling pathways and most widely used models to study their function.

Combined effect of GABA and glucagon-like peptide-1 receptor agonist on cytokine-induced apoptosis in pancreatic β-cell line and isolated human islets.

Background: Treatment with GABA or glucagon-like peptide-1 (GLP-1) can preserve pancreatic β-cell mass and prevent diabetes. Recently, we reported that the combination of GABA and sitagliptin (a dipeptidyl peptidase-4 inhibitor that increases endogenous GLP-1) was more effective than either agent alone in reducing drug-induced β-cell damage and promoting β-cell regeneration in mice. However, in human islets, it remains unclear whether GABA and GLP-1 exert similar effects.

Combined Oral Administration of GABA and DPP-4 Inhibitor Prevents Beta Cell Damage and Promotes Beta Cell Regeneration in Mice.

γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this hypothesis in a multiple low-dose streptozotocin (STZ)-induced beta cell injury mouse model (MDSD).

GABA promotes human β-cell proliferation and modulates glucose homeostasis.

γ-Aminobutyric acid (GABA) exerts protective and regenerative effects on mouse islet β-cells. However, in humans it is unknown whether it can increase β-cell mass and improve glucose homeostasis. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-γ mice with streptozotocin-induced diabetes.

Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.

Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER) positivity.

Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation.

The enhanced intestinal production of pro-inflammatory cytokines leads to inflammation and carcinogenesis, and therefore its down-regulation by nutrients could represent a promising therapeutic approach. We found for the first time that the secretion of interleukin-8 (IL-8) in intestinal epithelial cells stimulated by hydrogen peroxide or TNF-alpha was suppressed in the presence of carnosine (beta-Ala-His), a dietary dipeptide. Interestingly, carnosine had no influence on the stimulus-induced IL-8 mRNA expression, although the intracellular production and secretion of IL-8 were significantly inhibited by carnosine.

Food-derived peptides and intestinal functions.

The intestines are an important organ responsible for nutrient absorption, metabolism and recognition of food signals. The organ also acts as a physical and biological barrier against harmful substances including food pathogens and environmental chemicals. Food-derived peptides with a variety of physiological functions have been discovered in the past several decades.

Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells.

We investigated the effect of several amino acids on the secretion of such inflammatory cytokines as interleukin-8 (IL-8) induced by hydrogen peroxide or tumor necrosis factor-alpha (TNF-alpha) in intestinal epithelial-like Caco-2 and HT-29 cells. We found that histidine, one of the conditionally essential amino acids, significantly inhibited both hydrogen peroxide- and TNF-alpha-induced IL-8 secretion and mRNA expression in Caco-2 cells and HT-29 cells. These inhibitions were dose dependent and the inhibition rate of hydrogen peroxide-induced IL-8 secretion reached more than 50% at a concentration of 25mM, with over 95% inhibition at a concentration of 50mM.

Characterization of carnosine uptake and its physiological function in human intestinal epithelial Caco-2 cells.

Carnosine (beta-Ala-L-His) is known to have the physiological functions of an antioxidant. Although dietary carnosine is thought to be absorbed across intestinal epithelial cells, the mechanism for this absorption is not yet well understood and its function in the intestinal tract is also obscure. The intestinal transport of carnosine was characterized in the present study by using human intestinal Caco-2 cells, and its physiological function in these cells was further examined.