signaling pathways in elastic tissues

Abstract For many years elastin was considered as the matrix component structurally required to provide tissue elasticity. However, the expanded knowledge on the regulation of connective tissue homeostasis has revealed that elastic fibers also represent a source of elastokines and are the target of a number of signaling pathways mainly involving the TGF-β/BMP axis. A better understanding of these complex regulatory networks may pave the way for targeted therapeutic strategies in a number of genetic as well as acquired diseases and for the development of new functionalized biomaterials

Peach witches’-broom, an emerging disease associated with ‘Candidatus Phytoplasma phoenicium’ and ‘Candidatus Phytoplasma aurantifolia’ in Iran

During field surveys carried out from 2013 to 2017 in the eight main peach producing provinces of Iran, symptoms of a phytoplasma-like peach witches'-broom disease (PWIB), inducing severe yellowing, little leaf, internode shortening, crown and stem witches\u2019-broom, decline, and death, were observed. The aim of this work was to identify and characterize the agent(s) associated with PWIB by biological assays and molecular analyses. PWIB agents were successfully transmitted under controlled conditions from scions of in field-affected peach trees, exhibiting severe or mild symptoms, to peach and bitter almond seedlings inducing phytoplasma-like symptoms. A 16S rDNA fragment of 1250 bp was amplified by nested-PCR from all PWIB-affected trees and grafted seedlings. Nucleotide sequence identity, presence of species-specific signature sequences, in silico RFLP, single nucleotide polymorphisms, and phylogenetic analyses of 16S rDNA allowed the assignation of the phytoplasma strains identified in seven Iranian provinces in peach trees with severe PWIB symptoms to four SNP genetic lineages of \u2018Ca. P. phoenicium\u2019 (subgroup 16SrIX-B and its variant). PWIB phytoplasma strains identified in Abarkooh (Yazd province) in peach trees with mild symptoms were attributed to the species \u2018Ca. P. aurantifolia\u2019 (subgroup 16SrII-C). This report of a wide spread of \u2018Ca. P. phoenicium\u2019 in association with PWIB in Iran supported its capability of adaptation to a broad range of fruit tree species, such as peach, nectarine, and apricot. As \u2018Ca. P. phoenicium\u2019 and \u2018Ca. P. aurantifolia\u2019 are the etiological agents of other important plant diseases in Iran and neighbouring countries, further investigations are needed to determine the role played by peach in their epidemiological pathways

From Clinical Diagnosis to the Discovery of Multigene Rare Sequence Variants in Pseudoxanthoma elasticum: A Case Report

Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disease clinically characterised by early cutaneous alterations, and by late clinically relevant ocular, and cardiovascular manifestations. ABCC6 genetic tests are used to confirm clinical PXE diagnosis, but this strategy may be rather challenging when only one ABCC6 pathogenic variant is found. A next-generation sequencing approach focusing on 362 genes related to the calcification process and/or to inherited retinal diseases was performed on a patient with clinical PXE diagnosis (skin papules and laxity, angioid streaks, and atrophy) who was carrier of only one ABCC6 rare sequence variant. Beside ABCC6, several rare sequence variants were detected which can contribute either to the occurrence of calcification (GGCX and SERPINF1 genes) and/or to ophthalmological manifestations (ABCA4, AGBL5, CLUAP1, and KCNV2 genes). This wide-spectrum analysis approach facilitates the identification of rare variants possibly involved in PXE, thus avoiding invasive skin biopsy as well as expensive and time-consuming diagnostic odyssey and allows to broaden and to deepen the knowledge on this complex rare disease and to improve patients' counselling, also with a future perspective of personalised medicine

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Pseudoxanthoma elasticum (PXE) is a genetic disease considered as a paradigm of ectopic mineralization disorders, being characterized by multisystem clinical manifestations due to progressive calcification of skin, eyes, and the cardiovascular system, resembling an age-related phenotype. Although fibroblasts do not express the pathogenic ABCC6 gene, nevertheless these cells are still under investigation because they regulate connective tissue homeostasis, generating the “arena” where cells and extracellular matrix components can promote pathologic calcification and where activation of pro-osteogenic factors can be associated to pathways involving mitochondrial metabolism. The aim of the present study was to integrate structural and bioenergenetic features to deeply investigate mitochondria from control and from PXE fibroblasts cultured in standard conditions and to explore the role of mitochondria in the development of the PXE fibroblasts’ pathologic phenotype. Proteomic, biochemical, and morphological data provide new evidence that in basal culture conditions (1) the protein profile of PXE mitochondria reveals a number of differentially expressed proteins, suggesting changes in redox balance, oxidative phosphorylation, and calcium homeostasis in addition to modified structure and organization, (2) measure of oxygen consumption indicates that the PXE mitochondria have a low ability to cope with a sudden increased need for ATP via oxidative phosphorylation, (3) mitochondrial membranes are highly polarized in PXE fibroblasts, and this condition contributes to increased reactive oxygen species levels, (4) ultrastructural alterations in PXE mitochondria are associated with functional changes, and (5) PXE fibroblasts exhibit a more abundant, branched, and interconnected mitochondrial network compared to control cells, indicating that fusion prevail over fission events. In summary, the present study demonstrates that mitochondria are modified in PXE fibroblasts. Since mitochondria are key players in the development of the aging process, fibroblasts cultured from aged individuals or aged in vitro are more prone to calcify, and in PXE, calcified tissues remind features of premature aging syndromes; it can be hypothesized that mitochondria represent a common link contributing to the development of ectopic calcification in aging and in diseases. Therefore, ameliorating mitochondrial functions and cell metabolism could open new strategies to positively regulate a number of signaling pathways associated to pathologic calcification