- The MDCK cell line (Madin-Darby Canine Kidney) has significantly contributed to research on Helicobacter pylori pathogenesis, particularly in understanding epithelial cell polarity, tight junction integrity, and barrier function during infection. Unlike AGS cells, MDCK cells are derived from normal canine kidney epithelium and have the ability to form highly polarized monolayers with well-defined apical-basolateral polarity, tight junctions, adherens junctions, and desmosomes. These features make them a powerful in vitro system to study how H. pylori targets the epithelial barrier and disrupts intercellular junctions.
- One of the major uses of MDCK cells in H. pylori research is to investigate how the bacterium—especially the CagA effector protein—alters tight junction proteins such as ZO-1 and occludin, as well as adherens junction components like E-cadherin. Studies using MDCK cells have shown that upon infection, unphosphorylated CagA is recruited to sites of cell-cell contact, where it interacts with ZO-1 and JAM-A, leading to mislocalization of tight junction components and the formation of ectopic junctional complexes. These changes compromise the epithelial barrier, increasing permeability and facilitating bacterial access to deeper tissues.
- MDCK cells have also been essential in evaluating the functional consequences of junctional disruption. By using tracer molecules such as albumin or dextran, researchers have demonstrated that H. pylori infection leads to increased paracellular leakage, a hallmark of impaired barrier function. This has provided a mechanistic basis for understanding how H. pylori promotes chronic inflammation and tissue damage in the gastric mucosa.
- Moreover, due to their robust polarity, MDCK cells have been used to study apical versus basolateral delivery of bacterial factors, helping clarify how H. pylori adheres to the apical surface and injects CagA into host cells. Their use has also extended to dissecting the role of PAR1b (MARK2) in polarity regulation, which is another key target of CagA. Inhibition of PAR1b by CagA in MDCK cells results in loss of polarity, disruption of the cytoskeleton, and changes in cell shape—all of which mimic early oncogenic events in epithelial tissues.
- In addition to wild-type MDCK cells, genetically modified or reporter-expressing MDCK lines have been employed to track junctional protein dynamics, visualize cell-cell contacts, and monitor signaling pathway activation in real time during infection.
- In summary, the MDCK cell line has provided critical insights into how H. pylori disrupts epithelial architecture and function, complementing findings from cancer-derived lines like AGS. Its ability to model polarized epithelia and intact junctional complexes makes it especially valuable for studying the initial stages of infection, barrier compromise, and the host-pathogen interface at the cellular junctions.
