Scientific publications

Primary cilia control endothelial permeability by regulating expression and location of junction proteins

Wall shear stress (WSS) determines intracranial aneurysm (IA) development. Polycystic kidney disease (PKD) patients have a high IA incidence and risk of rupture. Dysfunction/absence of primary cilia in PKD endothelial cells (ECs) may impair mechano-transduction of WSS and favour vascular disorders. The molecular links between primary cilia dysfunction and IAs are unknown.

Osteoarthritis: Mechanistic Insights, Senescence, and Novel Therapeutic Opportunities

Osteoarthritis (OA) is the most common joint disease. In the last years, the research community has focused on understanding the molecular mechanisms that led to the pathogenesis of the disease, trying to identify different molecular and clinical phenotypes along with the discovery of new therapeutic opportunities. Different types of cell-to-cell communication mechanisms have been proposed to contribute to OA progression, including mechanisms mediated by connexin43 (Cx43) channels or by small extracellular vesicles.

Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related diseases such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin 43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage.

Expression and Functionality of Connexin-Based Channels in Human Liver Cancer Cell Lines

The present study investigated changes in connexin expression and gap junction functionality in liver cancer in vitro.

Connexins and Pannexins in Vascular Function and Disease

This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function.

Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals

Connexin-based channels play key roles in cellular communication and can be affected by deleterious chemicals. In this study, the effects of various genotoxic carcinogenic compounds, non-genotoxic carcinogenic compounds and non-carcinogenic compounds on the expression and functionality of connexin-based channels, both gap junctions and connexin hemichannels, were investigated in human hepatoma HepaRG cell cultures.

Genome wide CRISPR/Cas9 screen identifies the coagulation factor IX (F9) as a regulator of senescence

Here, using a functional genome-wide CRISPR/Cas9 genetic screen we found several genes that participate in the proliferation arrest induced by CDK4/6 inhibitors.

Effects of Drugs Formerly Proposed for COVID-19 Treatment on Connexin43 Hemichannels

Over the past two years, azithromycin, chloroquine, dexamethasone, favipiravir, hydroxychloroquine, lopinavir, remdesivir, ribavirin, and ritonavir have been proposed as drugs for the treatment of the coronavirus disease 2019 (COVID-19), which is associated with prominent systemic inflammation. The current study aimed to investigate if Cx43 hemichannels, being key players in inflammation, could be affected by these drugs which were formerly designated as COVID-19 drugs.

Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels

Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections. In the present study, we selected a panel of drugs previously tested in clinical trials as potential candidates for the treatment of COVID-19 early on in the pandemic, including hydroxychloroquine, chloroquine, azithromycin, dexamethasone, ribavirin, remdesivir, favipiravir, lopinavir, and ritonavir.

Lymphatic Connexins and Pannexins in Health and Disease

This review highlights current knowledge on the expression and function of connexins and pannexins, transmembrane channel proteins that play an important role in intercellular communication, in both the developing and mature lymphatic vasculature.

In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach

The liver is among the most frequently targeted organs by noxious chemicals of diverse nature. Liver toxicity testing using laboratory animals not only raises serious ethical questions, but is also rather poorly predictive of human safety towards chemicals.

Mechanisms Underlying Connexin Hemichannel Activation in Disease

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease.

Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection

Since the mid-20th century, ischemic heart disease has been the world’s leading cause of death. Developing effective clinical cardioprotection strategies would make a significant impact in improving both quality of life and longevity in the worldwide population.

Non-canonical roles of connexins

Gap junctions mediate cellular communication and homeostasis by controlling the intercellular exchange of small and hydrophilic molecules and ions. Gap junction channels are formed by the docking of 2 hemichannels of adjacent cells, which in turn are composed of 6 connexin subunits.

Connexin and pannexin (hemi)channels: emerging targets in the treatment of liver disease

Connexin proteins are the building blocks of hemichannels, which dock further between adjacent cells to form gap junctions. Gap junctions control the intercellular exchange of critical homeostasis regulators.

Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression.

Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis

Extracellular ATP is a central signaling molecule in inflammatory responses. Pannexin1 (Panx1) channels release ATP in a controlled manner and have been implicated in various inflammatory pathologies, but their role in atherogenesis remains elusive.