Volume 98 Issue 9, September 2018

NKX2-1 is the master transcription factor governing thyroid development and function. The authors used Nkx2-1(fl/fl);TPO-cre mice as a model to study in vivo regeneration and folliculogenesis of the thyroid. They found that NKX2-1 plays a role in differentiation through the modulation of the protein kinase AKT.

This report examined secreted exosomes from two in vitro cell culture models: an epithelial to mesenchymal transition model and a cancer stem-like cell model. The authors evaluated the expression and transfer of four long non-coding RNAs (HOTAIR, MALAT, PVT1, and linc-ROR) from exosomes derived from the models. They show that there is induced proliferation and invasive properties via the transfer of lncRNAs by exosomes.

This study elucidates alterations in DNA methylation patterns due to cross-talk between insulin and interleukin (IL)-6 signaling pathways in endothelial cells. The authors observed that IL-6-induced insulin resistance is associated with proteasomal degradation of DNA methyltransferase 1 and increased DNA synthesis, which subsequently leads to global DNA hypomethylation and differential methylation of promoters of genes involved in insulin signaling and angiogenesis.

This paper describes the relationship between heparin-binding epidermal growth factor (HB-EGF) and chronic obstructive pulmonary disease (COPD). HB-EGF expression is significantly increased in lung tissue of patients with COPD. In vitro, HB-EGF promotes collagen production in lung fibroblasts and induces epithelial-mesenchymal transition through induction of N-and E-cadherin, and vimentin expression. These results may provide insight into the underlying pathogenesis of COPD.

Mechanical ventilation may cause diaphragm weakness due to muscle injury and atrophy. This study shows that endotoxin-augmented mechanical ventilation-induced diaphragmatic injury occurs through the activation of toll-like receptor 4 and nuclear factor-κB signaling pathways. These findings may aid in the development of treatments for patients with sepsis.

Providing a high fat/calorie diet plus high fructose/glucose in drinking water is shown to be an optimal approach to induce nonalcoholic steatohepatitis in mice. The animal model shows remarkable necroptosis, steatosis, fibrosis and insulin resistance as well as a disordered profile of lipid metabolism and adipokines. This model should prove useful for pathophysiologic investigation and pharmacologic development.

This paper shows that thioredoxin-interacting protein (TXNIP) expression is significantly upregulated in kidneys after unilateral ureteral obstruction. TXNIP deficient mice showed significant protection from renal injury. The reduction in oxidative stress, interstitial inflammation, fibrosis, NLRP3 inflammasome activity and tubular cell apoptosis indicates that TXNIP may be a potential therapeutic target for renal fibrosis-associated kidney diseases.

In this study, the authors identified a transcription repressor, forebrain embryonic zinc finger 2 (Fezf2), as a potential prognostic marker for bladder cancer. Overexpression of Fezf2 inhibited the proliferation, migration, invasion, and angiogenesis of bladder cancer cells through the NF-κB signaling pathway, while knockdown of Fezf2 had the opposite effect. Thus, Fezf2 may play fundamental roles in bladder cancer progression.

Sex and diabetes affect angiotensin-converting enzyme (ACE) and ACE2 expression and are key determinants of kidney disease progression. Here the authors demonstrate that there are sex differences in the severity of angiotensin II (ANGII)-hypertension and diabetic nephropathy, the activation of the renin-angiotensin system cascade, and the crosstalk between ACE and ACE2 in vivo. This work increases our understanding of the sex-specific role of ACE2 and ACE in diabetic nephropathy, reinforcing the necessity of individualized treatments.