Choroid Plexus Connexin 43 Expression and Gap Junction Flexibility Are Associated with Clinical Features of Acute EAE

Jovanova-Nešić, Katica; Koruga, Djuro; Kojić, Dejan; Kostic, Vitana M.; Rakić, Ljubisav; Shoenfeld, Yehuda

doi:10.1111/j.1749-6632.2009.04658.x

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…Immunostaining analysis for connexin 43 and GFP from heart slides was conducted using primary connexin 43 rabbit polyclonal antibody (Santa Cruz Biotechnology, Santa Cruz, CA) or anti-GFP goat polyclonal antibody (Abcam, Cambridge, MA). 38 , 39 Nuclei were stained with DAPI (Invitrogen, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

Genome-wide Computational Analysis Reveals Cardiomyocyte-specific Transcriptional Cis-regulatory Motifs That Enable Efficient Cardiac Gene Therapy

Rincón

Sarcar²,

Danso-Abeam

et al. 2015

Molecular Therapy

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Gene therapy is a promising emerging therapeutic modality for the treatment of cardiovascular diseases and hereditary diseases that afflict the heart. Hence, there is a need to develop robust cardiac-specific expression modules that allow for stable expression of the gene of interest in cardiomyocytes. We therefore explored a new approach based on a genome-wide bioinformatics strategy that revealed novel cardiac-specific cis-acting regulatory modules (CS-CRMs). These transcriptional modules contained evolutionary-conserved clusters of putative transcription factor binding sites that correspond to a “molecular signature” associated with robust gene expression in the heart. We then validated these CS-CRMs in vivo using an adeno-associated viral vector serotype 9 that drives a reporter gene from a quintessential cardiac-specific α-myosin heavy chain promoter. Most de novo designed CS-CRMs resulted in a >10-fold increase in cardiac gene expression. The most robust CRMs enhanced cardiac-specific transcription 70- to 100-fold. Expression was sustained and restricted to cardiomyocytes. We then combined the most potent CS-CRM4 with a synthetic heart and muscle-specific promoter (SPc5-12) and obtained a significant 20-fold increase in cardiac gene expression compared to the cytomegalovirus promoter. This study underscores the potential of rational vector design to improve the robustness of cardiac gene therapy.

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Section: Methodsmentioning

confidence: 99%

Genome-wide Computational Analysis Reveals Cardiomyocyte-specific Transcriptional Cis-regulatory Motifs That Enable Efficient Cardiac Gene Therapy

Rincón

Sarcar²,

Danso-Abeam

et al. 2015

Molecular Therapy

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“…These channels are formed by two hemichannels that are composed of six connexin proteins [97]. GJs mediate intercellular communication, exchange of metabolites, electrolytes, and second messengers between adjacent epithelial cells [98][99][100].…”

Section: Intercellular Junctions In the Cpmentioning

confidence: 99%

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Solar

Zamani

Kubíčková

et al. 2020

Fluids Barriers CNS

212

142

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The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…Upon induction of experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis), the CPE undergoes numerous morphological and functional changes, including the reorganization of claudins [115]. In addition, EAE potentiates the expression of Cx43 in CPE and increases the thickness of GJ plaques in atomic force microscopy [167]. It is however unknown how this relates to the progression of the disease.…”

Section: Cxs At the Epithelial Bcsfb And Obrbmentioning

confidence: 99%

A new angle on blood–CNS interfaces: A role for connexins?

et al. 2014

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a b s t r a c tNeuronal signaling in the CNS depends on the microenvironment around synapses and axons. To prevent fluctuations in blood composition affecting the interstitial fluid and CSF, two barriers, the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB), are interposed between the blood and the brain/CSF compartment. Brain capillary endothelial cells (ECs) constitute the BBB whereas choroid plexus epithelial (CPE) cells form the BCSFB. The anatomical basis of these barriers is located at the level of an intercellular junctional complex that impedes paracellular diffusion. Tight and adherens junctions are known as the principal constituents of this junctional complex. Transmembrane connexins (Cxs) are the prime building blocks of plasma membrane hemichannels that combine to form intercellular gap junctions (GJ). Although Cxs co-exist within the junctional complex, their influence on tight/adherens junctions and their role in barrier function of BBB ECs and CPE has been mostly ignored. Here, we review current knowledge on the role of Cxs in the BBB, BCSFB and other interfaces that subside within the CNS. We conclude that Cxs are a rather unexplored but promising target for influencing CNS barrier function.

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Choroid Plexus Connexin 43 Expression and Gap Junction Flexibility Are Associated with Clinical Features of Acute EAE

Cited by 8 publications

References 23 publications

Genome-wide Computational Analysis Reveals Cardiomyocyte-specific Transcriptional Cis-regulatory Motifs That Enable Efficient Cardiac Gene Therapy

Genome-wide Computational Analysis Reveals Cardiomyocyte-specific Transcriptional Cis-regulatory Motifs That Enable Efficient Cardiac Gene Therapy

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

A new angle on blood–CNS interfaces: A role for connexins?

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