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Claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro

Asian journal of Andrology 2016年第4期18卷 620-626页

作者： mark j mccabe Caroline FH Foo Marcel E Dinger Peter M Smooker Peter G Stanton Male Fertility Regulation Laboratory Hudson Institute of Medical Research Monash Medical Centre Clayton Victoria 3168 Australia School of Applied Sciences Royal Melbourne Institute of Technology University Bundoora Victoria 3088 Australia Kinghorn Centre for Clinical Genomics Garvan Institute of Medical Research Darlinghurst New South Wales 2010 Australia St Vincent's Clinical School UNSW Sydney New South Wales 2052 Australia.

The Sertoli cell tight junction （T j） is the key component of the blood-testis barrier, where it sequesters developing germ cells undergoing spermatogenesis within the seminiferous tubules. Hormonally regulated claudin-11 is a critical transmembrane protein involved in barrier function and its murine knockout results in infertility. We aimed to assess quantitatively the significance of the contribution of claudin-11 to Tj function, in vitro, using siRNA-mediated gene silencing. We also conducted an analysis of the contribution of occludin, another intrinsic transmembrane protein of the Tj. Silencing of claudin-11 and/or occludin was conducted using siRNA in an immature rat Sertoli cell culture model. Transepithelial electrical resistance was used to assess quantitatively Tj function throughout the culture. Two days after siRNA treatment, cells were fixed for immunocytochemical localization of junction proteins or lyzed for RT-PCR assessment of mRNA expression. Silencing of claudin-11, occludin, or both resulted in significant decreases in Tj function of 55% （P 〈 0.01）, 51% （P 〈 0.01）, and 62% （P 〈 0.01）, respectively. Data were concomitant with significant decreases in mRNA expression and marked reductions in the localization of targeted proteins to the Sertoli cell Tj. We provide quantitative evidence that claudin-11 contributes significantly （P 〈 0.01） to Sertoli cell Tj function in vitro. Interestingly, occludin, which is hormonally regulated but not implicated in infertility until late adulthood, is also a significant （P 〈 0.01） contributor to barrier function. Our data are consistent with in vivo studies that clearly demonstrate a role for these proteins in maintaining normal Tj barrier structure and function.

关键词： blood-testis barrier claudin-11 occludin Sertoli cell tight junction siRNA

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Sternal metastasis-the forgotten column and its effect on thoracic spine stability

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World journal of Orthopedics 2017年第6期8卷 455-460页

作者： Robert Pearse Piggott mark Curtin Sudarshan Munigangaiah Mutaz jadaan john Patrick mccabe Aiden Devitt Department of Trauma and Orthopaedic Surgery Galway University Hospitalsthe West/North West Hospitals GroupHSE

Sternal metastases are not studied extensively in the literature. There is a paucity of information on their role in metastatic disease. The concept of the fourth column was described by Berg in 1993, and has been proven in case report, clinically and biomechanical studies. The role of the sternum as a support to the thoracic spine is well documented in the trauma patients, but not much is known about its role in cancer patients. This review examines what is known on the role of the fourth column. Following this we have identified two likely scenarios that sternal metastases may impact management:(1) sternal pathological fracture increases the mobility of the semi-rigid thorax with the loss of the biomechanical support of the sternum-rib-thoracic spine complex; and(2) a sternal metastasis increases the risk of fracture, and while being medical treated the thoracic spine should be monitored for acute kyphosis and neurological injury secondarily to the insufficiency of the fourth column.

关键词： Fourth column Sternal fracture Sternal metastasis Sternal-rib-thoracic spine complex Spine stability

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