@article{kruger_pridgen_taylor_garman_blikslager_2020, title={Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus}, volume={318}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00086.2019}, abstractNote={Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus, but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers in order to determine the effect of pre-treatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pre-treatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (p<0.05). Evaluation of the interepithelial tight junctions showed well defined membrane localization of occludin in lubiprostone-treated injured tissues. Pre-treatment of tissues with the NKCC1 inhibitor, bumetanide, blocked lubiprostone-induced increases in Isc and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target.}, number={4}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Kruger, Leandi and Pridgen, Tiffany A. and Taylor, Ellie R. and Garman, Katherine S. and Blikslager, Anthony T.}, year={2020}, month={Apr}, pages={G613–G623} }
 @article{krüger_gonzalez_pridgen_mccall_furstenberg_harnden_carnighan_cox_blikslager_garman_et al._2017, title={Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair}, volume={313}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00036.2017}, DOI={10.1152/ajpgi.00036.2017}, abstractNote={Esophageal injury is a risk factor for diseases such as Barrett's esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair.NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Krüger, Leandi and Gonzalez, Liara and Pridgen, Tiffany A. and McCall, Shannon J. and Furstenberg, Richard J. and Harnden, Ivan and Carnighan, Gwendolyn E. and Cox, Abigail M. and Blikslager, Anthony and Garman, Katherine S. and et al.}, year={2017}, month={Sep}, pages={G180–G191} }