Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries

Parthasarathi, Kaushik; Ichimura, Hideo; Monma, Eiji; Lindert, Jens; Quadri, Sadiqa K.; Issekutz, Andrew C.; Bhattacharya, Jahar

doi:10.1172/jci26605c1

Cited by 49 publications

(76 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inhibitory effect of gap junction expression on PMN migration appears to involve heterotypic (i.e. more than one type of connexin) cell communication and, in particular, has been attributed to gap junctions comprised Cx40 and Cx37 (Zahler et al 2003) and Cx43 (Parthasarathi et al 2006). More recently, the functional consequences of this inhibitory activity have been highlighted in APOE KO mice (a model of atherosclerosis) also deleted for Cx37, where lesion formation was substantially enhanced (Wong et al 2006).…”

Section: Sex Differences In Leukocyte Recruitmentmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

View full text Add to dashboard Cite

The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.

show abstract

Section: Sex Differences In Leukocyte Recruitmentmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…These peptides, respectively, bind the sequences VCYDKSFPISHVR and SRPTEKTIFII in extracellular loops 1 and 2 of Cx43 (Figure 1). Pretreatment of rat pulmonary vessels with Cx43 mimetic peptides abolished the spread of calcium waves through gap junctions and the induction of P-selectin expression in endothelial cells [38]. Consistent with this ex vivo finding, Sarieddine et al [40] investigated the therapeutic potential of anti-Cx43 treatment to modulate neutrophil recruitment in mice during acute lung inflammation evoked by LPS instillation.…”

Section: Connexins As Therapeutic Targetsmentioning

confidence: 74%

“…According to Parthasarathi et al [38], Cx43 has a role in the spread of this inflammatory response. Imaging of the intact perfused lung showed evidence of calcium waves that propagate along pulmonary vessels.…”

Section: Connexins and Acute Lung Inflammationmentioning

confidence: 99%

“…Bronchial epithelium Primary cultures IHC Human [5] Alveolar epithelium Primary cultures NB Rat [13] Tissue IF Rat [14] Tissue IF, WB Mouse [15] Submucosal Tissue IF Rat [14] Primary cultures NB Rat [13] Tissue ISH Mouse [12] Tissue IF, WB Mouse [15] Alveolar endothelium Tissue IF Mouse [38,40] Myoepithelial gland cells Tissue IF Mouse [4] Tracheal smooth muscle cells Tissue IF Rat [102] Bronchiolar smooth muscle cells Tissue IF Mouse [4,103] Fibroblasts Primary cultures NB, RT-PCR, WB Human [104,105] Cx45 Alveolar epithelium Tissue RT-PCR Mouse [12] Bronchiolar smooth muscle cells Tissue Cx45eGFP Mouse [103] Fibroblasts Primary cultures NB, RT-PCR Human [104] Cx46 Alveolar epithelium Tissue IF, WB Mouse [15] Tissue IF Rat [14] Cx: Connexin; Cx45eGFP: Mice expressing Cx45 fused with enhanced green fluorescent protein; IF: immunofluorescence; IHC: immunohistochemistry; ISH: in situ hybridization; NB: northern blot; RT-PCR: reverse transcription polymerase chain reaction; WB: western blot.…”

Section: Cx32mentioning

confidence: 99%

See 1 more Smart Citation

Connexins as therapeutic targets in lung disease

Losa

Chanson²,

Crespin³

2011

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

INTRODUCTION: The lung is a mechanically active system exposed to the external environment and is particularly sensitive to injury and inflammation. Studies have identified intercellular communication pathways that promote proper lung function in response to injury and disease. These pathways involve connexins (Cxs) and gap junctional intercellular communication (GJIC). AREAS COVERED IN THIS REVIEW: The functional expression of Cxs in airway epithelium and vasculature, under normal and pathological conditions, is reviewed. Inhibition of GJIC and/or silencing of Cxs have been shown to modulate the course of disease development. Cx-based channels: i) coordinate ciliary beating and fluid transport to promote clearance of particulates, ii) regulate secretion of pulmonary surfactant, in response to deep inhalation by interconnecting type I and type II alveolar epithelial cells, and iii) are key mediators of pro- and anti-inflammatory signalling by the pulmonary endothelium, in order to modulate leukocyte recruitment from the circulation. EXPERT OPINION: Cx-based channels play several central roles in promoting a regulated inflammatory response and facilitating lung repair, thus enabling the pulmonary epithelium and vasculature to behave as integrated systems. Several pathologies can disrupt the normal communication pathways required for proper lung function, including acute lung injury, asthma, cystic fibrosis, pulmonary fibrosis and cancer

show abstract

“…As junções do tipo Gap permitem a troca de metabólitos, íons e moléculas sinalizadoras entre células adjacentes (BRUZZONE et al, 1996;KUMAR;GILULA, 1996). São formadas por conexinas, proteínas que estabelecem conexão e permitem o acoplamento celular durante a propagação da sinalização, assumindo grande importância nas respostas mediadas pelo cálcio (FANCHAOUY et al, 2005;PARTHASARATHI et al, 2006) e assim, regulando o tônus vascular (BRISSET et al, 2009;CHRIST, 1996). Christ (1995) mostrou que a resposta desencadeada por alfa 1 -adrenoceptores envolve a participação de junções do tipo Gap.…”

Section: Discussão -101unclassified

Mecanismos celulares que influenciam a sinalização por receptores 1-adrenérgicos na carótida contra-lateral à lesão por cateter balão

Pereira¹

View full text Add to dashboard Cite

Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries

Cited by 49 publications

References 0 publications

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Connexins as therapeutic targets in lung disease

Mecanismos celulares que influenciam a sinalização por receptores 1-adrenérgicos na carótida contra-lateral à lesão por cateter balão

Contact Info

Product

Resources

About