Francesc Ventura

Institut d'Investigació Biomédica de Bellvitge

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José Luís Rosa

Institut d'Investigació Biomédica de Bellvitge

Ramón Bartrons

Weatherford College

Carolina Pimenta-Lopes

Institut d'Investigació Biomédica de Bellvitge

Cristina Sánchez‐de‐Diego

University of Wisconsin Carbone Cancer Center

José Antonio Valer

Institut d'Investigació Biomédica de Bellvitge

Santiago Ambrosio

Universitat de Barcelona

Eddie Rodríguez-Carballo

University of Geneva

Monica Cubillos‐Rojas

Institute for Research in Biomedicine

Gonzalo Sánchez‐Duffhues

Nanomaterials and Nanotechnology Research Center

Beatriz Gámez

University of Oxford

Cooperative Institutions

Universitat de Barcelona

178

Institut d'Investigació Biomédica de Bellvitge

102

Instituto de Salud Carlos III

Bellvitge University Hospital

Universitat Autònoma de Barcelona

Consejo Superior de Investigaciones Científicas

Centro de Investigación Biomédica en Red

Centre National de la Recherche Scientifique

Inserm

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

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Direct Binding of Smad1 and Smad4 to Two Distinct Motifs Mediates Bone Morphogenetic Protein-specific Transcriptional Activation ofId1 Gene

Journal of Biological Chemistry (2002)

Teresa López‐Rovira Elisabet Chalaux Joan Massagué José Luís Rosa Francesc Ventura

Bone morphogenetic proteins (BMPs) are potent inhibitors of myoblast differentiation and inducers of bone formation both in vivo and in vitro. Expression of Id1, a negative regulator of basic helix-loop-helix transcription factors, is up-regulated by BMPs and contributes to the antimyogenic effects of this family of cytokines. In this report, we have identified a specific BMP-2 immediate early response enhancer in the human Id1gene. Transcriptional activation of the enhancer was increased by overexpression of BMP-responsive Smads, and Smad4 and was completely abrogated in Smad4-deficient cells. Deletion analysis demonstrates that the responsive region is composed of two separate DNA binding elements, a set of overlapping GC boxes, which bind BMP-regulated Smads upon BMP stimulation, and three repeats of CAGAC boxes. Gel shift and oligonucleotide pull-down assays demonstrated that these two types of motifs were capable of binding their corresponding Smads. However, deletion or mutation of either DNA binding element was nonadditive, since disruption of either GC or CAGAC boxes resulted in complete or severe loss of BMP-2 responsiveness. These data suggest the simultaneous requirement of two independent DNA binding elements to allow functional cooperativity of BMP-regulated Smads and Smad4 in BMP-activated gene promoters.

Cooperativity

Transcription

10.1074/jbc.m106826200

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Citations (279)

Contribution of S6K1/MAPK Signaling Pathways in the Response to Oxidative Stress: Activation of RSK and MSK by Hydrogen Peroxide

PLoS ONE (2013)

Anna Maria Siebel Monica Cubillos‐Rojas Roberto Christ Vianna Santos Taiane Schneider Carla Denise Bonan

Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals’ knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2.

Ribosomal s6 kinase

10.1371/journal.pone.0075523

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Citations (18)

Dental Stem Cells SV40, a new cell line developed in vitro from human stem cells of the apical papilla

International Endodontic Journal (2022)

Diana Sanz‐Serrano Cristina Sánchez‐de‐Diego Montse Mercadé Francesc Ventura

Abstract Aim To establish and fully characterize a new cell line from human stem cells of the apical papilla (SCAPs) through immortalization with an SV40 large T antigen. Methodology Human SCAPs were isolated and transfected with an SV40 large T antigen and treated with puromycin to select the infected population. Expression of human mesenchymal surface markers CD73, CD90 and CD105 was assessed in the new cell line named Dental Stem Cells SV40 (DSCS) by flow cytometry at early and late passages. Cell contact inhibition and proliferation were also analysed. To evaluate trilineage differentiation, quantitative polymerase chain reaction and histological staining were performed. Results DSCS cell flow cytometry confirmed the expression of mesenchymal surface markers even in late passages [100% positive for CD73 and CD90 and 98.9% for CD105 at passage (P) 25]. Fewer than 0.5% were positive for haematopoietic cell markers (CD45 and CD34). DSCS cells also showed increased proliferation when compared to the primary culture after 48 h, with a doubling time of 23.46 h for DSCS cells and 40.31 h for SCAPs, and retained the capacity to grow for >45 passages (150 population doubling) and their spindle‐shaped morphology. Trilineage differentiation potential was confirmed through histochemical staining and gene expression of the chondrogenic markers SOX9 and COL2A1 , adipogenic markers CEBPA and LPL , and osteogenic markers COL1A1 and ALPL . Conclusions The new cell line derived from human SCAPs has multipotency, retains its morphology and expression of mesenchymal surface markers and shows higher proliferative capacity even at late passages (P45). DSCS cells can be used for in vitro study of root development and to achieve a better understanding of the regenerative mechanisms.

CD90

Stem cell marker

Cluster of differentiation

10.1111/iej.13887

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Citations (4)

Relationship Between Subclinical Rejection and Genotype, Renal Messenger RNA, and Plasma Protein Transforming Growth Factor–β1 Levels

Transplantation (2006)

Miguel Hueso Estanis Navarro Francesc Moreso Violeta Beltrán-Sastre Francesc Ventura

Background. Transforming growth factor (TGF)–β1 is increased in allograft rejection and its production is associated with single nucleotide polymorphisms (SNPs). Methods. The contribution of SNPs at codons 10 and 25 of the TGF-β1 gene to renal allograft damage was assessed in 6-month protocol biopsies and their association with TGF-β1 production. TGF-β1 genotypes were evaluated by polymerase chain reaction (PCR)/restriction fragment length polymorphism. Intragraft TGF-β1 messenger RNA (mRNA) was measured by real-time PCR and TGF-β1 plasma levels were assessed by enzyme-linked immunosorbent assay. Results. Eighty consecutive patients were included. Allele T at codon 10 (risk ratio, 6.7; P=0.02) and an episode of acute rejection before protocol biopsy (risk ratio, 6.2; P=0.01) were independent predictors of subclinical rejection (SCR). TGF-β1 plasma levels, but not those of TGF-β1 mRNA, were increased in patients with SCR (2.59 ng/mL ± 0.91 [n=22] vs. 2.05 ng/mL ± 0.76 [n=43]; P=0.01). There was no association between allele T and TGF-β1 plasma or intragraft levels. Conclusions. Allele T at codon 10 of the TGF-β1 gene is associated with a higher incidence of SCR.

Subclinical infection

10.1097/01.tp.0000206102.67063.24

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Citations (13)

Tris-Acetate Polyacrylamide Gradient Gels for the Simultaneous Electrophoretic Analysis of Proteins of Very High and Low Molecular Mass

Methods in molecular biology (2018)

Monica Cubillos‐Rojas Fabiola Amair‐Pinedo Irantzu Tato Ramón Bartrons Francesc Ventura

Polyacrylamide

Coomassie Brilliant Blue

Molecular mass

10.1007/978-1-4939-8793-1_22

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Citations (7)

Differential Effects of Secreted and Soluble α-Klotho Expression Over Mineral Metabolism and Bone Microstructure

SSRN Electronic Journal (2022)

Joan Roig-Soriano Cristina Sánchez‐de‐Diego Jon Esandi-Jauregui Sergi Verdés Assumpció Bosch

α-Klotho protein is a promising candidate for treating age-associated deficits, due to pleiotropic beneficial effects. Previous experiments showed an osteoporotic phenotype after overexpressing the processed KL isoform (p-KL), characterized by reduced Pi and Ca2+ ions in blood and elevated levels of FGF23. In this work, we analyzed the effect of the secreted KL isoform (s-KL) over ion metabolism to assess the safety profile of this protein. We expressed independently both isoforms using gene therapy, and after eight weeks, animals receiving only p-KL (but not s-KL) treatment presented deleterious effects. Mice treated with s-KL vector, presented levels of Pi and Ca2+, FGF23 expression levels, bone microstructure and physical properties comparable to Null-treated mice. As a conclusion, s-KL (but not p-KL) is a safe therapeutic strategy to exploit KL antiaging protective effects, presenting no apparent negative effects over mineral metabolism and bone microstructure.Funding Information: This project was supported by the Ministerio Ciencia Innovación, Retos Sociedad (PID2019- 104034RB-I00), and the “Redes de Investigación Cooperativa Orientadas a Resultados en Salud"(RICORS) of the Carlos III Institute of Health (RD21/0017/0008). J.R is a recipient of an FI fellowship by the AGAUR (2018FI_B00657).Declaration of Interests: Portions of this work are the subject of a patent application held by the Universitat Autonoma de Barcelona (UAB, Spain); the Universitat de Barcelona (UB, Spain); the Institucio Catalana de Recerca i Estudis Avançats (ICREA, Spain); and the Vall d'Hebron Institute of Research (VHIR, Spain).Ethics Approval Statement: All experimental procedures involving animals were performed following standard ethical guidelines of the European Communities Council Directive 86/609/EEC and by the Institutional Animal Care and Use Committee of the Universitat Autònoma de Barcelona (M0348-DO5, procedure code P1 - 4882) and biosecurity procedure HR-265-16.

Klotho

Bone remodeling

10.2139/ssrn.4188431

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Citations (0)

In Vitro Characterization of an Anodized Surface of a Dental Implant Collar and Dental Abutment on Peri-Implant Cellular Response

Materials (2023)

Valeria Traver-Méndez Octavi Camps‐Font Francesc Ventura Miquel Angel Nicolau-Sansó Carles Subirà-Pifarré

The purpose of this paper was to determine the effect of anodization on the in vitro proliferation and adhesion of immortalized human keratinocytes (HaCats) and mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) in Titanium Grade 23 (Ti6Al4V ELI) discs and to describe the surface topography, roughness, and composition of dental implants (body and collar) and abutments submitted to an area-specific anodization process. HaCat cells and BM-MSCs were seeded onto discs with three different surface treatments: machined, area-specific anodization for abutments, and area-specific anodization for implant collars. Cell proliferation was assessed using a resazurin-based fluorescent dye on days 1, 3, and 7, while cell adhesion was examined using scanning electron microscopy (SEM). Surface topography, roughness, and composition were evaluated for six implant bodies with an anodized rough surface, six anodized implant smooth collars, and six anodized prosthetic abutments. Both HaCats and BM-MSCs showed increased viability over time (p < 0.001) with no statistically significant differences among the different surfaces (p = 0.447 HaCats and p = 0.631 BM-MSCs). SEM analysis revealed an enhanced presence and adhesion of HaCat cells on the anodized surface for the implant collars and an increased adhesion of BM-MSCs on both the anodized and machined surface abutments. The topography characteristics of the treated implants and abutments varied depending on the specific implant region. Chemical analysis confirmed the presence of oxygen, calcium, phosphorus, and sodium on the anodized surfaces. The area-specific anodization process can be utilized to create variable topography, increase the specific surface area, and introduce oxygen, calcium, phosphorus, and sodium to dental implants and abutments. While BM-MSCs and HaCat cells showed similar adhesion and proliferation on anodized and machined surfaces, a positive interaction between anodized Ti6Al4V ELI surfaces and these two cell lines present in the peri-implant mucosa was observed. Due to the limitations of the present study, further research is necessary to confirm these findings.

Anodizing

Collar

10.3390/ma16176012

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Citations (2)

The p38/MK2/Hsp25 Pathway Is Required for BMP-2-Induced Cell Migration

PLoS ONE (2011)

Cristina Gamell Antonio G. Susperregui Ora Bernard José Luís Rosa Francesc Ventura

Background Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. Methodology/Principal Findings Activation of p38 MAPK has been shown to be relevant for a number of BMP-2′s physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38α or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. Conclusions These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

CDC42

BMPR2

Lamellipodium

10.1371/journal.pone.0016477

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Citations (41)

Monitoring of pesticides in drinking and related waters in NE Spain with a multiresidue SPE-GC–MS method including an estimation of the uncertainty of the analytical results

Journal of Chromatography A (2001)

Jordi Quintana Isabel Martı́Francesc Ventura

Simazine

Solid phase extraction

10.1016/s0021-9673(01)01168-2