Colonic crypt stem cell functions are controlled by tight junction protein claudin-7 through Notch/Hippo signaling.

The tight junction protein claudin-7 is essential for tight junction function and intestinal homeostasis. Cldn7 deletion in mice leads to an inflammatory bowel disease-like phenotype exhibiting severe intestinal epithelial damage, weight loss, inflammation, mucosal ulcerations, and epithelial hyperplasia. Claudin-7 has also been shown to be involved in cancer metastasis and invasion.

Three-Dimensional Culture of Murine Colonic Crypts to Study Intestinal Stem Cell Function Ex Vivo.

The intestinal epithelium regenerates every 5-7 days, and is controlled by the intestinal epithelial stem cell (IESC) population located at the bottom of the crypt region. IESCs include active stem cells, which self-renew and differentiate into various epithelial cell types, and quiescent stem cells, which serve as the reserve stem cells in the case of injury. Regeneration of the intestinal epithelium is controlled by the self-renewing and differentiating capabilities of these active IESCs.

Trans-Compartmental Regulation of Tight Junction Barrier Function.

Tight junctions (TJs) are the most apical components of junctional complexes in epithelial and endothelial cells. Barrier function is one of the major functions of TJ, which restricts the ions and small water-soluble molecules from passing through the paracellular pathway. Adherens junctions (AJs) play an important role in cell-cell adhesion and cell signaling.

Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy.

Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin-matrix interactions. However, it is increasingly recognized that resident cell junction proteins can be found in varying locations and with previously unrecognized functions. Our study here presents the nanoarchitecture and nanocolocalization of cell junction proteins in culture and tissue by stochastic optical reconstruction microscopy (STORM).

Polymorphisms in () are Linked to Infection and Osteoporosis in Rheumatoid Arthritis.

We previously discovered that single nucleotide polymorphisms (SNPs) in (T-cell negative-regulators) occur in 78% of rheumatoid arthritis (RA), along with (MAP) infection in 33% of patients. In Crohn's disease, we reported that SNPs in and receptors () benefited intracellular MAP-survival, increased infection, and elevated inflammatory response mimicking the poor response to anti-TNF treatment in some patients. Here, we studied the frequency and effects of SNPs in in RA including gene expression, MAP infection, and osteoporosis marker levels in blood (54 RA and 48 healthy controls).

Mycobacterial infection influences bone biomarker levels in patients with Crohn's disease.

Patients with Crohn's disease (CD) have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocalcin in CD patients and cow-disease model (Johne's disease).