Transforming growth factor-beta and fibrosis.

International audienceTransforming growth factor-beta (TGF-beta), a prototype of multifunctional cytokine, is a key regulator of extracellular matrix (ECM) assembly and remodeling. Specifically, TGF-beta isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-beta expression in affected organs, and subsequent deregulation of TGF-beta functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-beta receptors. In particular, Smad proteins, TGF-beta receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both in vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes

Comment modéliser les événements de la fibrose cutanée ?

Classiquement, les fibroses cutanées sont considérées comme l’étape ultime d’un processus inflammatoire chronique et persistant, qui pérennise l’hyperplasie et la différenciation fibroblastique ainsi que l’accumulation de matrice extracellulaire. Le retentissement clinique de ces fibroses s’exprime tant au niveau esthétique que fonctionnel, et se révèle d’autant plus problématique qu’il n’existe à ce jour ni régression spontanée, ni thérapeutique antifibrosante efficace et sûre. Le développement et le maintien de la fibrose cutanée impliquent les différents composants cellulaires de la peau ainsi que plusieurs médiateurs paracrines, qui activent différentes voies de signalisation intracellulaires : ce réseau d’interaction est complexe et difficile à modéliser. Cette revue présente les modèles cellulaires et expérimentaux permettant de modéliser la fibrose cutanée, et expose leurs apports dans la compréhension des mécanismes physiopathologiques de fibrogenèse cutanée. Ces modèles constituent des outils performants pour tester de nouvelles hypothèses mécanistiques et thérapeutiques.Skin fibrosis is classically seen as the consequence of chronic inflammation and altered healing response that is characterized by the differentiation of fibroblasts into secretory myofibroblasts and accumulation of connective tissue. Although fibrosis severely affects organ function and causes esthetic defects, no effective therapy is currently available to attenuate the fibrogenic process probably because the fibrogenic process is more complex than previously thought. Indeed, it might involve several interacting and mutually dependent cell types (fibroblasts, keratinocytes, endothelial cells, inflammatory cells), numerous paracrine factors, bio-active molecules and micro-environmental stimuli (growth factors, vasoactive peptides, balance between pro- and anti-inflammatory cytokines, coagulation system, reactive oxygen species, extracellular matrix…). In this perspective, the traditional approach that model individual cell response in simple cell culture system is probably inadequate and too simplistic. This article reviews the new models used to study skin fibrosis in vitro, in organotypic culture systems and in vivo and examines how these different models might be used to identify new molecular pathways involved in fibrogenesis. The monolayer cultures allow the study of fibrogenic signals induced by a single factor on a single cell type. Isolation of cells from fibrotic tissue allows to define the fibrogenic differentiation acquired in vivo. The organotypic models allow cell to cell and cell to matrix interaction and the experimental models in pigs and mice allowed studies in integrated physiological systems. These various and complementary models would also provide new tools to develop and test new drugs and treatments

Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin-1beta in human tendon-derived cells

To determine whether the fluoroquinolone antibiotic ciprofloxacin, which can cause tendon pain and rupture in a proportion of treated patients, affects the expression of matrix metalloproteinases (MMPs) in human tendon-derived cells in culture. Cell cultures were derived from 6 separate tendon explants, and were incubated in 6-well culture plates for 2 periods of 48 hours each, with ciprofloxacin (or DMSO in controls) and interleukin-1ß (IL-1ß), alone and in combination. Samples of supernatant medium from the second 48-hour incubation were assayed for MMPs 1, 2, and 3 by Western blotting. RNA was extracted from the cells and assayed for MMP messenger RNA (mRNA) by semiquantitative reverse transcription–polymerase chain reaction, with normalization for GAPDH mRNA. Unstimulated tendon cells expressed low or undetectable levels of MMP-1 and MMP-3, and substantial levels of MMP-2. IL-1ß induced a substantial output of both MMP-1 and MMP-3 into cell supernatants, reflecting increases (typically 100-fold) in MMP mRNA, but had only minor effects on MMP-2 expression. Ciprofloxacin had no detectable effect on MMP output in unstimulated cells. Preincubation with ciprofloxacin potentiated IL-1ß–stimulated MMP-3 output, reflecting a similar effect on MMP-3 mRNA expression. Ciprofloxacin also potentiated IL-1ß–stimulated MMP-1 mRNA expression, but did not potentiate the output of MMP-1, and had no significant effects on MMP-2 mRNA expression or output. Ciprofloxacin can selectively enhance MMP expression in tendon-derived cells. Such effects might compromise tendon microstructure and integrity

Analyse des flux de matières pour la modélisation agricole - Vers la scénarisation d'alternatives

National audienc

Biochar fracture resistance

Biochar is a brittle material that tends to break under mechanical stress. This could be an advantage if it is intended to obtain a char powder, but it is typically unwanted since it generates dust that induce biochar losses or even explosion risk. Mechanical stresses are typically observed inside pyrolysis reactors (Scala et al., 2006), during transport/storage and finally inside the soil (Spokas et al., 2014). There are few data in the literature regarding the mechanical strength of char (Capon et al., 1980). This study aims at assessing the impact of pyrolysis temperature and biomass species on fracture resistance. Please click on the file below for full content of the abstract

Depolymerization of fractionated wood by hydrothermal liquefaction

Direct thermochemical conversion of lignocellulosic biomass produces a mixture of compounds that have to be separated to produce purified building blocks. Moreover, lignin derived products have a detrimental effect on further biological conversion processes, such as fermentation. For all these reasons, it is important to develop an integrated approach for a better fractionation and valorisation of macromolecules (carbohydrates and lignin) in bio-refineries. Please click Additional Files below to see the full abstract

Biomass to oil : fast pyrolysis and subcritical hydrothermal liquefaction

International audienceThe present abstract deals with the comparison of two biomass-to-oil processes: fast pyrolysis and subcritical hydrothermal liquefaction. Using the same biomass (beech sawdust), fast pyrolysis was led thanks to the cyclone reactor (wall temperature between 870 and 1040 K) and subcritical hydrothermal liquefaction thanks to a 150-ml-batch-reactor (temperature between 420 and 600 K). Mass balances and analysis (ultimate analysis, HHV, pH, Karl-Fischer, gas chromatographies, H 1 NMR) allow the comparison of both processes and the characterization of the main fractions of pyro-oils (heavy oils, light oils and aerosols) and liq-oils (heavy oils and water soluble organics)

Batch fermentation of d-glucose/cellobiose mixtures by clostridium acetobutylicum atcc 824: energetic and carbon source regulation

Lignocellulosic biomass presents an interesting alternative to fossil carbon sources as a source of renewable energy that respects the environment. Indeed, this abundant resource can be converted by a wide range of thermal, chemical and biological techniques to compounds that can be used as substrate in anaerobic fermentation to produce biofuels and building blocks. As a general rule, micro-organisms possess regulation mechanisms that ensure the sequential use of the carbon and energy sources present in their environment. These regulations may consequently play a vital role in biomass to energy and building blocks conversion performances. Clostridium acetobutylicum, a promising biomass transformation organism, has the capacity to utilize a wide variety of compounds as carbon and energy sources. These compounds may be present in a complex mixture produced from cellulose conversion. Therefore it is of high importance to understand the potential synergy or inhibiting effects of the cellulose-derived products. The aim of this work is to study this regulation mechanism by using glucose and cellobiose as model substrates, provided alone and in mixtures to Clostridium acetobutylicum. Our experiments show a total consumption of both substrates, alone or in mixtures, with an increment of 30% of microbial growth production of cellobiose over glucose. A diauxic growth (cell growth in two phases) occurs in the presence of different mixtures of D-glucose and cellobiose. In general, D-glucose is the preferred substrate and after its complete consumption, when exhausted, the growth kinetics exhibits an adaptation time, of approximately 1-2 hours, before to be able to use cellobiose (figure 1). This adaptation is probably due to an induction stage that is also accompanied of acid consumption (lactic acid). This study provides a first approach to understand the metabolic changes related to substrate utilization in Clostridia. Please click Additional Files below to see the full abstract