Volume 98 Issue 11, November 2018

In this report, the authors sought to determine whether expression of cadherin 11 in mesenchymal cells plays a critical role in ear morphogenesis. Cadherin 11 knockout mice show moderate hearing loss. The air-filled area of auditory bulla is reduced and residual mesenchymal cells are observed in the middle ear. This mutant mouse may be a promising animal model for elucidating the causes of conductive hearing loss.

Homeostasis of the corneal epithelium is critical in exerting a barrier function to noxious external stimuli. This study shows that that plakoglobin, a member of the catenin protein family, is essential to the maintenance of homeostasis of the corneal epithelium in mice. Corneal epithelium-specific deletion of the plakoglobin gene impairs tissue integrity against mechanical intervention and also suppresses wound healing without affecting cell proliferation.

GLI transcription factors, which mediate the Hedgehog pathway, are over-expressed in cervical cancer. RNA interference reveals an essential role of GLI2, but not GLI3, in promoting proliferation and migration and xenograft tumor growth of human cervical cancer cells. Mechanistically, the function of GLI2 is mediated by protein kinase B (AKT), and may be targeted as a novel therapeutic strategy.

The authors aimed to identify epigenetic aberrations involving microRNAs (miRNAs) whose genes become hypermethylated in endometrial primary tumors. They found that that miR-137 is hypermethylated and loses expression in human endometrial tumors. Increasing miR-137 expression suppresses endometrial cancer cell growth in vitro and xenograft tumor growth in nude mice, partly because miR-137 targets EZH2, which participates in histone methylation, and LSD1, a histone demethylation enzyme.

Macrophage-epithelial crosstalk regulates cell cycle progression and is essential for the maintenance of a healthy epithelial phenotype. In the present work, the authors show that macrophage-secreted lipocalin-2 is crucial in rescuing epithelial cells from cell cycle arrest and in promoting epithelial proliferation through inhibition of peroxisome proliferator-activated receptor (PPAR)-γ. Lipocalin-2 maintains the epithelial cytoskeleton structure via megalin and downstream activation of thePI3K/AKT signaling pathway.

The dysregulation of dermal fibroblast proliferation and apoptosis is thought to be related to hypertrophic scar formation. In this study, the authors show that the balance of autophagy in HSF is critical for fibrosis formation, and both downregulation and excessive upregulation of autophagy inhibits collagen expression via wild type p53 and the pro-survival protein Bcl-xL.

This study investigated whether quantitative computer-extracted images of tissue of lymph node (LN)-, estrogen receptor (ER)+ breast cancer could help stratify patients into discrete outcome groups. The results suggest that quantitative histomorphometric features of nuclear shape and orientation are strongly and independently predictive of patient survival in ER+, LN- breast cancer.

In this study the authors demonstrate that the secretin/secretin receptor axis plays a regulatory role in biliary proliferation and liver fibrosis through differential changes in the senescence of cholangiocytes and hepatic stellate cells in a mouse model of primary sclerosing cholangitis. Targeting senescent cholangiocytes by modulation of the secretin/secretin receptor axis may provide a key therapeutic approach in the treatment of cholestatic liver diseases.

The bile acid rsodeoxycholic acid (UDCA) is the choice of treatment for primary biliary cholangitis patients with abnormal liver enzymes; however, its mechanism is not clear, and is the focus of this investigation. Bile acids alter mast cell (MC) histamine release. Following liver injury, such as that seen in primary sclerosing cholangitis, MCs infiltrate the liver. MC-derived histamine increases biliary damage, fibrosis, and inflammation. UDCA treatment decreases these parameters via reduced MC activation.

Damage to the airway epithelium can be caused by numerous environmental factors. This study describes the development and characterization of a wound healing model from nasal epithelial cells grown at the air-liquid interface. It also identifies the rate of wound closure from healthy donors and the effect epidermal growth factor receptor inhibition has on wound healing.

This paper describes the enrichment of rare neoplastic Hodgkin and Reed-Sternberg (HRSC) cells of classical Hodgkin lymphoma (cHL) from the archival formalin-fixed and paraffin-embedded tissues. This technique allows enrichment of HRSC from 1-5% in the initial cHL tissue to 40-80% in sorted populations, which enables robust genetic analysis of cHL by targeted high throughput sequencing and array-CGH.

Hepatocytic Bcl6 regulates sex-specific drug metabolism in the liver. In this paper the authors found that expression of male-dominant or female-dominant cytochrome P450 is altered in Bcl6 liver-specific knockout mice. Serum sex hormones and fertility did not change in these mice, suggesting that in this mouse model the effects are exclusively liver-specific.