Cell-matrix interactions in cultured dermal fibroblasts from patients with an inherited connective-tissue disorder

Contri, M. Baccarani; Tiozzo, Roberta; Croce, Maria Antonietta; Andreoli, Tiziana; Paepe, Anne De

doi:10.1007/bf00746072

Cited by 6 publications

(3 citation statements)

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“…In agreement with biochemical ¢ndings, the immunohistochemical analysis showed alterations a¡ecting PG content and distribution in PXE-a¡ected cell layers [11,14]. Furthermore, preliminary studies from our laboratory showed abnormal cytoskeletal organization in PXE ¢broblasts which might be suggestive for altered cell-matrix interactions [15].…”

Section: Discussionsupporting

confidence: 85%

“…Actually, PXE ¢broblasts produce families of proteoglycans with higher molecular weights compared to controls [11] and which di¡er from controls also for their sulfation characteristic [14]. Moreover, preliminary results, on in vitro cultured cells, seem to indicate that PXE ¢broblasts are characterized by peculiar cytoskeletal structures, consistent with the hypothesis of altered cell-matrix interactions [15].…”

Section: Pseudoxanthoma Elasticum (Pxe) Is An Inherited Connective Ti...supporting

confidence: 66%

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Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE)

Quaglino

Boraldi

Barbieri

et al. 2000

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Pseudoxanthoma elasticum (PXE) is a genetic connective tissue disease, whose gene and pathogenesis are still unknown. Dermal fibroblasts from patients affected by PXE have been compared in vitro with fibroblasts taken from sex and age-matched normal individuals. Cells were grown and investigated in monolayer, into three-dimensional collagen gels and in suspension. Compared with normal cells, PXE fibroblasts cultured in monolayer entered more rapidly within the S phase and exhibited an increased proliferation index; on the contrary, similarly to normal fibroblasts, PXE cells did not grow in suspension. Furthermore, compared with normal fibroblasts, PXE cells exhibited lower efficiency in retracting collagen type I lattices and lower adhesion properties to collagen type I and to plasma fibronectin. This behavior was associated with higher expression of integrin subunits alpha2, alpha5, alphav, whereas beta1 subunit as well as alpha2beta1 and alpha5beta1 integrin expression was lower than in controls. Compared to controls, PXE fibroblasts had higher CAM protein expression in accordance with their high tendency to form cellular aggregates, when kept in suspension. The demonstration that PXE fibroblasts have altered cell-cell and cell-matrix interactions, associated with modified proliferation capabilities, is consistent with the hypothesis that the gene responsible for PXE might have a broad regulatory role on the cellular machinery.

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Section: Discussionsupporting

confidence: 85%

Section: Pseudoxanthoma Elasticum (Pxe) Is An Inherited Connective Ti...supporting

confidence: 66%

Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE)

Quaglino

Boraldi

Barbieri

et al. 2000

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…In PXE, dermal fibroblasts are characterized by changes in cytoskeletal organization (Baccarani Contri et al, 1993) and in cell-matrix interactions (Quaglino et al, 2000). These differences can influence the mitochondria, and it is well known that the mitochondria can modify their functions, depending also on the local qualitative and quantitative characteristics of the extracellular matrix (i.e., glycosaminoglycans, elastinassociated components, proteolytically degraded peptides) (Tiozzo Costa et al, 1988;Gheduzzi et al, 2005) through an interconnected sensory system involving cell-matrix interactions and cytoskeletal components (de Cavanagh et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Lofaro

Boraldi

García-Fernández

et al. 2020

Front. Cell Dev. Biol.

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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.

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Characterization of dermal myofibroblast differentiation in pseudoxanthoma elasticum

Faust

Donhauser

Fischer

et al. 2017

Experimental Cell Research

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Cell-matrix interactions in cultured dermal fibroblasts from patients with an inherited connective-tissue disorder

Cited by 6 publications

References 4 publications

Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE)

Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE)

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Characterization of dermal myofibroblast differentiation in pseudoxanthoma elasticum

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