Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts
Abstract
:1. Introduction
2. Results
2.1. Differential Expression of Genes in Untreated and Acidic-Bile-Salt-Treated HEMF
2.1.1. Extracellular Molecules
2.1.2. Plasma Membrane Molecules
2.1.3. Validation of RNA Sequencing Genes with RT-PCR
2.2. Functional Analysis of DEGs
2.2.1. Identification of Canonical Pathways Activated in Acidic-Bile-Salt-Treated HEMFs
2.2.2. Diseases and Biological Functions
2.2.3. Upstream Analysis: Identification of Upstream Regulators and Causal Networks
2.2.4. Inhibition of HEMF-Derived CXCL-8, but Not HEMF-Derived AREG Inhibits Squamous Epithelial Cell Proliferation
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. HEMF Treatment with Acidic Bile Salt Mixture
4.3. RNA Sequencing Expression Profiling and Pathway Analysis of Gene Networks
4.4. RNA Isolation and RT-PCR
4.5. ELISA
4.6. Proliferation Assay
4.7. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- El-Serag, H.B.; Sweet, S.; Winchester, C.C.; Dent, J. Update on the epidemiology of gastro-oesophageal reflux disease: A systematic review. Gut 2014, 63, 871–880. [Google Scholar] [CrossRef] [PubMed]
- Katzka, D.A.; Pandolfino, J.E.; Kahrilas, P.J. Phenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet. Clin. Gastroenterol. Hepatol. 2020, 18, 767–776. [Google Scholar] [CrossRef] [PubMed]
- Kia, L.; Pandolfino, J.E.; Kahrilas, P.J. Biomarkers of Reflux Disease. Clin. Gastroenterol. Hepatol. 2016, 14, 790–797. [Google Scholar] [CrossRef] [PubMed]
- Ronkainen, J.; Aro, P.; Storskrubb, T.; Johansson, S.E.; Lind, T.; Bolling-Sternevald, E.; Graffner, H.; Vieth, M.; Stolte, M.; Engstrand, L.; et al. High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: A Kalixanda study report. Scand. J. Gastroenterol. 2005, 40, 275–285. [Google Scholar] [CrossRef] [PubMed]
- Richter, J.E.; Rubenstein, J.H. Presentation and Epidemiology of Gastroesophageal Reflux Disease. Gastroenterology 2018, 154, 267–276. [Google Scholar] [CrossRef] [PubMed]
- Hayeck, T.J.; Kong, C.Y.; Spechler, S.J.; Gazelle, G.S.; Hur, C. The prevalence of Barrett’s esophagus in the US: Estimates from a simulation model confirmed by SEER data. Dis. Esophagus 2010, 23, 451–457. [Google Scholar] [CrossRef] [PubMed]
- Savarino, E.; Zentilin, P.; Savarino, V. NERD: An umbrella term including heterogeneous subpopulations. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 371–380. [Google Scholar] [CrossRef]
- Souza, R.F.; Huo, X.; Mittal, V.; Schuler, C.M.; Carmack, S.W.; Zhang, H.Y.; Zhang, X.; Yu, C.; Hormi-Carver, K.; Genta, R.M.; et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology 2009, 137, 1776–1784. [Google Scholar] [CrossRef]
- Farre, R. Pathophysiology of gastro-esophageal reflux disease: A role for mucosa integrity? Neurogastroenterol. Motil. 2013, 25, 783–799. [Google Scholar] [CrossRef]
- Sharma, P.; Yadlapati, R. Pathophysiology and treatment options for gastroesophageal reflux disease: Looking beyond acid. Ann. N. Y. Acad. Sci. 2021, 1486, 3–14. [Google Scholar] [CrossRef]
- Tack, J.; Pandolfino, J.E. Pathophysiology of Gastroesophageal Reflux Disease. Gastroenterology 2018, 154, 277–288. [Google Scholar] [CrossRef] [PubMed]
- Dunbar, K.B.; Agoston, A.T.; Odze, R.D.; Huo, X.; Pham, T.H.; Cipher, D.J.; Castell, D.O.; Genta, R.M.; Souza, R.F.; Spechler, S.J. Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA 2016, 315, 2104–2112. [Google Scholar] [CrossRef] [PubMed]
- Kahrilas, P.J. Turning the Pathogenesis of Acute Peptic Esophagitis Inside Out. JAMA 2016, 315, 2077–2078. [Google Scholar] [CrossRef]
- Vieth, M.; Mastracci, L.; Vakil, N.; Dent, J.; Wernersson, B.; Baldycheva, I.; Wissmar, J.; Ruth, M.; Fiocca, R. Epithelial Thickness is a Marker of Gastroesophageal Reflux Disease. Clin. Gastroenterol. Hepatol. 2016, 14, 1544–1551.e1. [Google Scholar] [CrossRef] [PubMed]
- Blevins, C.H.; Iyer, P.G.; Vela, M.F.; Katzka, D.A. The Esophageal Epithelial Barrier in Health and Disease. Clin. Gastroenterol. Hepatol. 2018, 16, 608–617. [Google Scholar] [CrossRef]
- Kessing, B.F.; Bredenoord, A.J.; Weijenborg, P.W.; Hemmink, G.J.; Loots, C.M.; Smout, A.J. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am. J. Gastroenterol. 2011, 106, 2093–2097. [Google Scholar] [CrossRef] [PubMed]
- Jovov, B.; Que, J.; Tobey, N.A.; Djukic, Z.; Hogan, B.L.; Orlando, R.C. Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am. J. Gastroenterol. 2011, 106, 1039–1047. [Google Scholar] [CrossRef]
- Orlando, R.C. How good is the neosquamous epithelium? Dig. Dis. 2014, 32, 164–170. [Google Scholar] [CrossRef]
- Gargus, M.; Niu, C.; Vallone, J.G.; Binkley, J.; Rubin, D.C.; Shaker, A. Human esophageal myofibroblasts secrete proinflammatory cytokines in response to acid and Toll-like receptor 4 ligands. Am. J. Physiol. Gastrointest. Liver Physiol. 2015, 308, G904–G923. [Google Scholar] [CrossRef]
- Gargus, M.; Niu, C.; Shaker, A. Isolation of myofibroblasts from mouse and human esophagus. J. Vis. Exp. 2015, 18, 52215. [Google Scholar] [CrossRef] [Green Version]
- Shaker, A.; Binkley, J.; Darwech, I.; Swietlicki, E.; McDonald, K.; Newberry, R.; Rubin, D.C. Stromal cells participate in the murine esophageal mucosal injury response. Am. J. Physiol. Gastrointest. Liver Physiol. 2013, 304, G662–G672. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Niu, C.; Yang, K.; Shaker, A. Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth. Sci. Rep. 2018, 8, 12354. [Google Scholar] [CrossRef] [PubMed]
- Hu, L.; Zhang, C.; Yang, K.; Li, M.; Shaker, A. Human esophageal myofibroblasts increase squamous epithelial thickness via paracrine mechanisms in an in vitro model of gastroesophageal reflux disease. PLoS ONE 2020, 15, e0238852. [Google Scholar] [CrossRef] [PubMed]
- Niu, C.; Chauhan, U.; Gargus, M.; Shaker, A. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line. PLoS ONE 2016, 11, e0153185. [Google Scholar] [CrossRef] [PubMed]
- Lin, H.; Lee, E.; Hestir, K.; Leo, C.; Huang, M.; Bosch, E.; Halenbeck, R.; Wu, G.; Zhou, A.; Behrens, D.; et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 2008, 320, 807–811. [Google Scholar] [CrossRef] [PubMed]
- Nagayama, S.; Iiizumi, M.; Katagiri, T.; Toguchida, J.; Nakamura, Y. Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas. Oncogene 2004, 23, 5551–5557. [Google Scholar] [CrossRef]
- Wang, D.H.; Clemons, N.J.; Miyashita, T.; Dupuy, A.J.; Zhang, W.; Szczepny, A.; Corcoran-Schwartz, I.M.; Wilburn, D.L.; Montgomery, E.A.; Wang, J.S.; et al. Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett’s metaplasia. Gastroenterology 2010, 138, 1810–1822. [Google Scholar] [CrossRef]
- Robertson, I.B.; Horiguchi, M.; Zilberberg, L.; Dabovic, B.; Hadjiolova, K.; Rifkin, D.B. Latent TGF-beta-binding proteins. Matrix Biol. 2015, 47, 44–53. [Google Scholar] [CrossRef]
- Seman, M.; Adriouch, S.; Haag, F.; Koch-Nolte, F. Ecto-ADP-ribosyltransferases (ARTs): Emerging actors in cell communication and signaling. Curr. Med. Chem. 2004, 11, 857–872. [Google Scholar] [CrossRef]
- Turk, V.; Stoka, V.; Turk, D. Cystatins: Biochemical and structural properties, and medical relevance. Front. Biosci. 2008, 13, 5406–5420. [Google Scholar] [CrossRef] [Green Version]
- Guo, Q.; Zhu, L.; Wang, C.; Wang, S.; Nie, X.; Liu, J.; Liu, Q.; Hao, Y.; Li, X.; Lin, B. SERPIND1 Affects the Malignant Biological Behavior of Epithelial Ovarian Cancer via the PI3K/AKT Pathway: A Mechanistic Study. Front. Oncol. 2019, 9, 954. [Google Scholar] [CrossRef] [PubMed]
- Simone, T.M.; Higgins, C.E.; Czekay, R.P.; Law, B.K.; Higgins, S.P.; Archambeault, J.; Kutz, S.M.; Higgins, P.J. SERPINE1: A Molecular Switch in the Proliferation-Migration Dichotomy in Wound-“Activated” Keratinocytes. Adv. Wound Care 2014, 3, 281–290. [Google Scholar] [CrossRef] [PubMed]
- Furuta, G.T.; Katzka, D.A. Eosinophilic Esophagitis. N. Engl. J. Med. 2015, 373, 1640–1648. [Google Scholar] [CrossRef] [PubMed]
- Rawson, R.; Yang, T.; Newbury, R.O.; Aquino, M.; Doshi, A.; Bell, B.; Broide, D.H.; Dohil, R.; Kurten, R.; Aceves, S.S. TGF-beta1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. J. Allergy Clin. Immunol. 2016, 138, 791–800.e4. [Google Scholar] [CrossRef]
- Williamson, P.; Proudfoot, J.; Gharibans, A.; Dohil, L.; Newbury, R.; Barsamian, J.; Hassan, M.; Rawson, R.; Katzka, D.; Kurten, R.; et al. Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis. Clin. Gastroenterol. Hepatol. 2022, 20, 57–64.e3. [Google Scholar] [CrossRef]
- Monard, D. SERPINE2/Protease Nexin-1 in vivo multiple functions: Does the puzzle make sense? Semin. Cell Dev. Biol. 2017, 62, 160–169. [Google Scholar] [CrossRef]
- Lelios, I.; Cansever, D.; Utz, S.G.; Mildenberger, W.; Stifter, S.A.; Greter, M. Emerging roles of IL-34 in health and disease. J. Exp. Med. 2020, 217, e20190290. [Google Scholar] [CrossRef]
- Nagano, K. R-spondin signaling as a pivotal regulator of tissue development and homeostasis. Jpn. Dent. Sci. Rev. 2019, 55, 80–87. [Google Scholar] [CrossRef]
- Cesar-Razquin, A.; Snijder, B.; Frappier-Brinton, T.; Isserlin, R.; Gyimesi, G.; Bai, X.; Reithmeier, R.A.; Hepworth, D.; Hediger, M.A.; Edwards, A.M.; et al. A Call for Systematic Research on Solute Carriers. Cell 2015, 162, 478–487. [Google Scholar] [CrossRef]
- Busslinger, G.A.; Weusten, B.L.A.; Bogte, A.; Begthel, H.; Brosens, L.A.A.; Clevers, H. Human gastrointestinal epithelia of the esophagus, stomach, and duodenum resolved at single-cell resolution. Cell Rep. 2021, 34, 108819. [Google Scholar] [CrossRef]
- Hagenbuch, B.; Stieger, B. The SLCO (former SLC21) superfamily of transporters. Mol. Asp. Med. 2013, 34, 396–412. [Google Scholar] [CrossRef] [PubMed]
- Pizzagalli, M.D.; Bensimon, A.; Superti-Furga, G. A guide to plasma membrane solute carrier proteins. FEBS J. 2021, 288, 2784–2835. [Google Scholar] [CrossRef] [PubMed]
- Hediger, M.A.; Clemencon, B.; Burrier, R.E.; Bruford, E.A. The ABCs of membrane transporters in health and disease (SLC series): Introduction. Mol. Asp. Med. 2013, 34, 95–107. [Google Scholar] [CrossRef] [PubMed]
- Nakajima, K.I.; Zhu, K.; Sun, Y.H.; Hegyi, B.; Zeng, Q.; Murphy, C.J.; Small, J.V.; Chen-Izu, Y.; Izumiya, Y.; Penninger, J.M.; et al. KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis. Nat. Commun. 2015, 6, 8532. [Google Scholar] [CrossRef] [PubMed]
- Schaap, F.G.; Trauner, M.; Jansen, P.L. Bile acid receptors as targets for drug development. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 55–67. [Google Scholar] [CrossRef]
- Farr, L.; Ghosh, S.; Moonah, S. Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair. Front. Immunol. 2020, 11, 1273. [Google Scholar] [CrossRef]
- Kordass, T.; Osen, W.; Eichmuller, S.B. Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E. Front. Immunol. 2018, 9, 813. [Google Scholar] [CrossRef]
- Kania, A.; Klein, R. Mechanisms of ephrin-Eph signalling in development, physiology and disease. Nat. Rev. Mol. Cell Biol. 2016, 17, 240–256. [Google Scholar] [CrossRef]
- Landrier, J.F.; Eloranta, J.J.; Vavricka, S.R.; Kullak-Ublick, G.A. The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G476–G485. [Google Scholar] [CrossRef]
- Capello, A.; Moons, L.M.; Van de Winkel, A.; Siersema, P.D.; van Dekken, H.; Kuipers, E.J.; Kusters, J.G. Bile acid-stimulated expression of the farnesoid X receptor enhances the immune response in Barrett esophagus. Am. J. Gastroenterol. 2008, 103, 1510–1516. [Google Scholar] [CrossRef]
- De Gottardi, A.; Dumonceau, J.M.; Bruttin, F.; Vonlaufen, A.; Morard, I.; Spahr, L.; Rubbia-Brandt, L.; Frossard, J.L.; Dinjens, W.N.; Rabinovitch, P.S.; et al. Expression of the bile acid receptor FXR in Barrett’s esophagus and enhancement of apoptosis by guggulsterone in vitro. Mol. Cancer 2006, 5, 48. [Google Scholar] [CrossRef]
- Hong, J.; Behar, J.; Wands, J.; Resnick, M.; Wang, L.J.; DeLellis, R.A.; Lambeth, D.; Souza, R.F.; Spechler, S.J.; Cao, W. Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma. Gut 2010, 59, 170–180. [Google Scholar] [CrossRef] [PubMed]
- Britsch, S. The neuregulin-I/ErbB signaling system in development and disease. Adv. Anat. Embryol. Cell Biol. 2007, 190, 1–65. [Google Scholar] [PubMed]
- Yarden, Y.; Pines, G. The ERBB network: At last, cancer therapy meets systems biology. Nat. Rev. Cancer 2012, 12, 553–563. [Google Scholar] [CrossRef]
- Compton, C.C.; Warland, G.; Nakagawa, H.; Opitz, O.G.; Rustgi, A.K. Cellular characterization and successful transfection of serially subcultured normal human esophageal keratinocytes. J. Cell. Physiol. 1998, 177, 274–281. [Google Scholar] [CrossRef]
- Kasagi, Y.; Chandramouleeswaran, P.M.; Whelan, K.A.; Tanaka, K.; Giroux, V.; Sharma, M.; Wang, J.; Benitez, A.J.; DeMarshall, M.; Tobias, J.W.; et al. The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes. Cell. Mol. Gastroenterol. Hepatol. 2018, 5, 333–352. [Google Scholar] [CrossRef]
- Liu, T.; Zhang, X.; So, C.K.; Wang, S.; Wang, P.; Yan, L.; Myers, R.; Chen, Z.; Patterson, A.P.; Yang, C.S.; et al. Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells. Carcinogenesis 2007, 28, 488–496. [Google Scholar] [CrossRef]
- Kandulski, A.; Jechorek, D.; Caro, C.; Weigt, J.; Wex, T.; Monkemuller, K.; Malfertheiner, P. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn. Aliment. Pharmacol. Ther. 2013, 38, 643–651. [Google Scholar] [CrossRef]
- Kandulski, A.; Malfertheiner, P. Gastroesophageal reflux disease—From reflux episodes to mucosal inflammation. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 15–22. [Google Scholar] [CrossRef]
- Ha, H.; Debnath, B.; Neamati, N. Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics 2017, 7, 1543–1588. [Google Scholar] [CrossRef]
- Guo, Y.; Zang, Y.; Lv, L.; Cai, F.; Qian, T.; Zhang, G.; Feng, Q. IL8 promotes proliferation and inhibition of apoptosis via STAT3/AKT/NFkappaB pathway in prostate cancer. Mol. Med. Rep. 2017, 16, 9035–9042. [Google Scholar] [CrossRef] [PubMed]
- Meng, L.; Zhao, Y.; Bu, W.; Li, X.; Liu, X.; Zhou, D.; Chen, Y.; Zheng, S.; Lin, Q.; Liu, Q.; et al. Bone mesenchymal stem cells are recruited via CXCL8-CXCR2 and promote EMT through TGF-beta signal pathways in oral squamous carcinoma. Cell Prolif. 2020, 53, e12859. [Google Scholar] [CrossRef] [PubMed]
- Linge, H.M.; Collin, M.; Nordenfelt, P.; Morgelin, M.; Malmsten, M.; Egesten, A. The human CXC chemokine granulocyte chemotactic protein 2 (GCP-2)/CXCL6 possesses membrane-disrupting properties and is antibacterial. Antimicrob. Agents Chemother. 2008, 52, 2599–2607. [Google Scholar] [CrossRef] [PubMed]
- Liu, G.; An, L.; Zhang, H.; Du, P.; Sheng, Y. Activation of CXCL6/CXCR1/2 Axis Promotes the Growth and Metastasis of Osteosarcoma Cells in vitro and in vivo. Front. Pharmacol. 2019, 10, 307. [Google Scholar] [CrossRef]
- Zheng, S.; Shen, T.; Liu, Q.; Liu, T.; Tuerxun, A.; Zhang, Q.; Yang, L.; Han, X.; Lu, X. CXCL6 fuels the growth and metastases of esophageal squamous cell carcinoma cells both in vitro and in vivo through upregulation of PD-L1 via activation of STAT3 pathway. J. Cell. Physiol. 2021, 236, 5373–5386. [Google Scholar] [CrossRef]
- Khurram, S.A.; Bingle, L.; McCabe, B.M.; Farthing, P.M.; Whawell, S.A. The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour. J. Oral Pathol. Med. 2014, 43, 667–674. [Google Scholar] [CrossRef]
- Wang, D. Discrepancy between mRNA and protein abundance: Insight from information retrieval process in computers. Comput. Biol. Chem. 2008, 32, 462–468. [Google Scholar] [CrossRef]
- Liu, Y.; Beyer, A.; Aebersold, R. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 2016, 165, 535–550. [Google Scholar] [CrossRef]
- Singh, B.; Carpenter, G.; Coffey, R.J. EGF receptor ligands: Recent advances. F1000Research 2016, 5. [Google Scholar] [CrossRef]
- Berasain, C.; Avila, M.A. Amphiregulin. Semin. Cell Dev. Biol. 2014, 28, 31–41. [Google Scholar] [CrossRef]
- Merchant, N.B.; Rogers, C.M.; Trivedi, B.; Morrow, J.; Coffey, R.J. Ligand-dependent activation of the epidermal growth factor receptor by secondary bile acids in polarizing colon cancer cells. Surgery 2005, 138, 415–421. [Google Scholar] [CrossRef] [PubMed]
- Riese, D.J., 2nd; Cullum, R.L. Epiregulin: Roles in normal physiology and cancer. Semin. Cell Dev. Biol. 2014, 28, 49–56. [Google Scholar] [CrossRef] [PubMed]
- Avissar, N.E.; Toia, L.; Hu, Y.; Watson, T.J.; Jones, C.; Raymond, D.P.; Matousek, A.; Peters, J.H. Bile acid alone, or in combination with acid, induces CDX2 expression through activation of the epidermal growth factor receptor (EGFR). J. Gastrointest. Surg. 2009, 13, 212–222. [Google Scholar] [CrossRef] [PubMed]
- Bao, Y.; Zhang, S.; Guo, Y.; Wei, X.; Zhang, Y.; Yang, Y.; Zhang, H.; Ma, M.; Yang, W. Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma. Clin. Transl. Oncol. 2018, 20, 1185–1195. [Google Scholar] [CrossRef]
- Pang, C.; LaLonde, A.; Godfrey, T.E.; Que, J.; Sun, J.; Wu, T.T.; Zhou, Z. Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences. Clin. Exp. Gastroenterol. 2017, 10, 29–37. [Google Scholar] [CrossRef] [PubMed]
- Vogel, C.; Marcotte, E.M. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat. Rev. Genet. 2012, 13, 227–232. [Google Scholar] [CrossRef]
- Johnson, J.M.; Castle, J.; Garrett-Engele, P.; Kan, Z.; Loerch, P.M.; Armour, C.D.; Santos, R.; Schadt, E.E.; Stoughton, R.; Shoemaker, D.D. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 2003, 302, 2141–2144. [Google Scholar] [CrossRef]
- Huo, X.; Zhang, H.Y.; Zhang, X.I.; Lynch, J.P.; Strauch, E.D.; Wang, J.Y.; Melton, S.D.; Genta, R.M.; Wang, D.H.; Spechler, S.J.; et al. Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett’s esophagus. Gastroenterology 2010, 139, 194–203.e1. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Patankar, M.; Li, M.; Khalatbari, A.; Castle, J.D.; Hu, L.; Zhang, C.; Shaker, A. Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts. Int. J. Mol. Sci. 2022, 23, 10371. https://doi.org/10.3390/ijms231810371
Patankar M, Li M, Khalatbari A, Castle JD, Hu L, Zhang C, Shaker A. Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts. International Journal of Molecular Sciences. 2022; 23(18):10371. https://doi.org/10.3390/ijms231810371
Chicago/Turabian StylePatankar, Madhura, Meng Li, Atousa Khalatbari, Joshua D. Castle, Liping Hu, Chunying Zhang, and Anisa Shaker. 2022. "Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts" International Journal of Molecular Sciences 23, no. 18: 10371. https://doi.org/10.3390/ijms231810371