The interactome of transglutaminase-2 in kidney fibrosis: uncovering a mechanism for TG2 unconventional secretion in chronic kidney disease

Increased release and activity of transglutaminase-2 (TG2) in the tubulointerstitial space has been correlated with the progression of kidney fibrosis during chronic kidney disease (CKD), a condition for which there is no cure. TG2 extracellular activity contributes to kidney fibrosis by determining matrix deposition and resistance to degradation, through calcium dependent protein transamidation and matrix recruitment of latent TGF-β1, however, the mechanism of TG2 secretion from kidney cells is still unknown. This study aims at elucidating the mechanism of TG2 trafficking in CKD as a way to control its release and ultimately limit fibrosis progression. The murine unilateral ureteric obstruction (UUO) model of renal fibrosis was employed. Firstly, the UUO proteome was resolved and the effect of TG2-KO elucidated by quantitative proteomics of kidney homogenates. This led to the identification of markers of CKD strongly upregulated at an advanced stage of UUO, some of which were dysregulated in TG2-null kidneys, and allowed to set a background for subsequent analyses. Secondly, the TG2 interactome was generated by developing an original approach, based on quantitative mass spectrometry of TG2 immunoprecipitates. This highlighted a significant association of TG2 with a large cluster of vesicular proteins which increased post-UUO, forming the hypothesis that TG2 could be secreted by extracellular vesicles (EV) in CKD. The hypothesis was tested in a model of established tubular epithelial cells (TEC), which revealed TG2 in EV mainly of intraluminal origin (exosomes). The involvement of cell surface heparan sulfate proteoglycan (HSPG) syndecan-4 in the secretion pathway of TG2 was also investigated, and a dual role was ascribed to the proteoglycan, supporting both TG2 secretion and extracellular retention of the enzyme, with promotion of TGF-β1 activation. In conclusion, this study has shown a novel Sdc4-dependent secretion pathway for TG2 by TECs via extracellular vesicles, which is relevant to CKD condition

Heavy Metal Pollutions: State of the Art and Innovation in Phytoremediation

Mineral nutrition of plants greatly depends on both environmental conditions, particularly of soils, and the genetic background of the plant itself. Being sessile, plants adopted a range of strategies for sensing and responding to nutrient availability to optimize development and growth, as well as to protect their metabolisms from heavy metal toxicity. Such mechanisms, together with the soil environment, meaning the soil microorganisms and their interaction with plant roots, have been extensively studied with the goal of exploiting them to reclaim polluted lands; this approach, defined phytoremediation, will be the subject of this review. The main aspects and innovations in this field are considered, in particular with respect to the selection of efficient plant genotypes, the application of improved cultural strategies, and the symbiotic interaction with soil microorganisms, to manage heavy metal polluted soils

Spotlight on the transglutaminase 2-heparan sulfate interaction

Heparan sulfate proteoglycans (HSPGs), syndecan-4 (Sdc4) especially, have been suggested as potential partners of transglutaminase-2 (TG2) in kidney and cardiac fibrosis, metastatic cancer, neurodegeneration and coeliac disease. The proposed role for HSPGs in the trafficking of TG2 at the cell surface and in the extracellular matrix (ECM) has been linked to the fibrogenic action of TG2 in experimental models of kidney fibrosis. As the TG2-HSPG interaction is largely mediated by the heparan sulfate (HS) chains of proteoglycans, in the past few years a number of studies have investigated the affinity of TG2 for HS, and the TG2 heparin binding site has been mapped with alternative outlooks. In this review, we aim to provide a compendium of the main literature available on the interaction of TG2 with HS, with reference to the pathological processes in which extracellular TG2 plays a role

Características agronômicas dos acessos do Banco Ativo de Germoplasma de Uva.

Este trabalho teve por objetivo caracterizar agronomicamente 19 acessos do Banco Ativo de Germoplasma de Uva (BAGUva), por um período compreendido entre sete e 11 anos. Os materiais são cultivados a campo, em condições padronizadas, sob porta-enxerto '101-14?, com sistema de sustentação em espaldeira e poda em Guyot. Foram avaliadas características relacionadas ao cacho, à baga, à produtividade e à incidência das principais doenças da videira no país

Endomembrane reorganization induced by heavy metals

Plant cells maintain plasmatic concentrations of essential heavy metal ions, such as iron, zinc, and copper, within the optimal functional range. To do so, several molecular mechanisms have to be committed to maintain concentrations of non-essential heavy metals and metalloids, such as cadmium, mercury and arsenic below their toxicity threshold levels. Compartmentalization is central to heavy metals homeostasis and secretory compartments, finely interconnected by traffic mechanisms, are determinant. Endomembrane reorganization can have unexpected effects on heavy metals tolerance altering in a complex way membrane permeability, storage, and detoxification ability beyond gene\u2019s expression regulation. The full understanding of endomembrane role is propaedeutic to the comprehension of translocation and hyper-accumulation mechanisms and their applicative employment. It is evident that further studies on dynamic localization of these and many more proteins may significantly contribute to the understanding of heavy metals tolerance mechanisms. The aim of this review is to provide an overview about the endomembrane alterations involved in heavy metals compartmentalization and tolerance in plants

The role of the multidisciplinary evaluation of interstitial lung diseases: Systematic literature review of the current evidence and future perspectives

The opportunity of a multidisciplinary evaluation for the diagnosis of interstitial pneumonias highlighted a major change in the diagnostic approach to diffuse lung disease. The new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guidelines for the diagnosis of idiopathic pulmonary fibrosis have reinforced this assumption and have underlined that the exclusion of connective tissue disease related lung involvement is mandatory, with obvious clinical and therapeutic impact. The multidisciplinary team discussion consists in amoment of interaction among the radiologist, pathologist and pulmonologist, also including the rheumatologist when considered necessary, to improve diagnostic agreement and optimize the definition of those cases in which pulmonary involvement may represent the first or prominent manifestation of an autoimmune systemic disease. Moreover, the proposal of classification criteria for interstitial lung disease with autoimmune features (IPAF) represents an effort to define lung involvement in clinically undefined autoimmune conditions. The complexity of autoimmune diseases, and in particular the lack of classification criteria defined for pathologies such as anti-synthetase syndrome, makes the involvement of the rheumatologist essential for the correct interpretation of the autoimmune element and for the application of classification criteria, that could replace clinical pictures initially interpreted as IPAF in defined autoimmune disease, minimizing the risk of misdiagnosis. The aim of this review was to evaluate the available evidence about the efficiency and efficacy of different multidisciplinary team approaches, in order to standardize the professional figures and the core set procedures that should be necessary for a correct approach in diagnosing patients with interstitial lung disease

Caracterização da qualidade do mosto de acessos do Banco Ativo de Germoplasma de Uva.

O objetivo deste trabalho foi avaliar a qualidade do mosto, com relação ao pH, conteúdo de sólidos solúveis totais (SS) e acidez total titulável (ATT) de 19 acessos do Banco Ativo de Germoplasma de Uva

Características agronômicas dos acessos do Banco Ativo de Germoplasma de Uva da Embrapa Uva e Vinho.

A caracterização de acessos de uva mantidos em coleção é uma etapa importante, que contribui para o melhoramento genético. Este trabalho teve como objetivo caracterizar agronomicamente 43 acessos do Banco Ativo de Germoplasma de Uva (BAG-Uva), mantido pela Embrapa Uva e Vinho, localizada em Bento Gonçalves-RS

Avaliação físico-química de acessos do Banco Ativo de Germoplasma de Uva (BAG-Uva).

O objetivo deste trabalho é caracterizar 43 acessos do BAG-Uva, com relação à qualidade do mosto [pH, Sólidos Solúveis Totais (SS) e Acidez Total Titulável (ATT)], por um período que variou entre sete e 10 anos. Trinta e oito acessos também foram avaliados com relação ao Índice de Polifenóis Totais (IPT) e conteúdo de antocianinas (ANT), por um período que variou de dois e três anos

The role of ABC1K7 and ABC1K8, two ABC1K kinases of Arabidopsis thaliana

The activity of bc1 complex kinases (ABC1K) belong to a large group of atypical protein kinases found in prokaryotes and eukaryotes. In bacteria and mitochondria, ABC1K kinases are involved in the respiratory pathway, being necessary for the synthesis of the coenzyme Q. In chloroplasts, ABC1K proteins play a role in prenylquinone synthesis and stress responses, but their precise function remains unclear. A functional characterization was carried out for ABC1K7 and ABC1K8, two ABC1K proteins of the Arabidopsis thaliana plastome. The comparison of abc1k7 and abc1k8 mutants, abc1k7/abc1k8 double mutant and wild-type plants revealed a reduction in plastidial ironcontaining proteins of the Cytb6f complex in the mutants. Iron uptake from soil is not hampered in mutant lines, suggesting that ABC1K7 and ABC1K8 affect iron distribution within the chloroplast. Moreover, mutant plants accumulated more ferritin and superoxide, and showed reduced tolerance to reactive oxygen species (ROS). Because ROS take part in abscisic acid (ABA) signaling, we investigated the relation between ABA and ABC1K7 and ABC1K8 and found that both genes were upregulated by ABA treatment, while expression of several ABA-responsive genes resulted affected in mutants. Moreover, analyzing ABA-mediated processes, we determined that germination was more affected by ABA treatment and osmotic and salt stress in the single and double mutants than in wild-type plants. Stomatal aperture was also reduced in the mutants under standard growth conditions and was not further reduced by exogenous ABA application. Furthermore, ABA-induced senescence symptoms were more severe in the leaves of the mutants compared to wild type leaves. Taken together, these data suggest that ABC1K7 and ABC1K8 probably act in signaling pathways that influence responses to ROS production and oxidative stress, such as ABA signaling, probably by influencing the cellular redox state and chloroplast lipid metabolism