Volume 101 Issue 2, February 2021

Epithelial-to-mesenchymal transition of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. In the present study, the miR-184/TP63 axis modulates the TGF-β1-induced fibrotic alterations in epithelial cell lines and bleomycin-induced pulmonary fibrosis in mice, confirming that miR-184/TP63 axis is involved in IPF progression.

The authors investigated the clinicopathologic significance of microRNA-130b expression and analyzed its cancer-specific functions using a cancer cell line. High microRNA-130b expression was associated with adverse clinicopathologic parameters and poor patient outcomes. In vitro, downregulation of microRNA-130b caused a decrease in cell proliferation, migration, and invasion. Hence, miR-130b is a potential therapeutic target for lung cancer.

Abnormal expression of myocardial infarction-related transcription factor 2 (Mirt2) is associated with myocardial infarction, cardiomyocyte apoptosis and oxidative stress in rats with acute myocardial infarction (AMI). These effects involve the miR-764/PDK1/AKT axis. Therefore, the current findings provide a theoretical basis for the diagnosis and treatment of clinical myocardial infarction by monitoring changes in Mirt2 levels.

In this study, the authors provide evidence that ectopic expression of oncogenic mutant Kras in pancreatic ducts generates early and late (PanIN) and pancreatic ductal adenocarcinoma (PDAC) . They characterized this Ras rheostat model which reveals elevated Kras mutation frequency and loss of PTEN are important drivers of PanIN and invasive ductal derived PDAC.

Chronic stress can change hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in nonalcoholic steatohepatitis mice, disrupting bile acid homeostasis by induction of hepatic Cyp7a1 expression. This study describes a new role βMCA in the liver, indicating its potential usefulness for nonalcohol fatty liver disease therapy.

The authors report the feasibility of generating, expanding, and enumerating viable patient-derived intraductal papillary mucinous neoplasm (IPMN) tumor and normal pancreatic organoids from fresh and cryopreserved resected tissue. Organoids were characterized histologically and genomically and recapitulated the morphological and mutational profiles of resected IPMNs, suggesting promise of organoids for translational efforts.

SECISBP2 overexpression is an independent negative prognostic predictor in diffuse large B-cell lymphoma. Additionally, SECISBP2 positively correlates with selenoprotein expression. In vitro, SECISBP2 knockout increases intracellular reactive oxygen species accumulation via the downregulation of selenoproteins, inhibiting cell growth and promoting cell death after doxorubicin treatment. Therefore, SECISBP2 is a potential therapeutic target for malignant lymphoma.

C-X-C chemokine receptor type 5 (CXCR5) regulates retinal pigment epithelium (RPE) homeostasis through PI3K/AKT signaling and by suppression of FOXO1 activation. CXCR5-deficency leads to decreased RPE differentiation, compromised barrier function, and increase in epithelial-mesenchymal transition markers (αSMA, N-cadherin, and vimentin) in CXCR5-deficient RPE cells in vitro and in CXCR5^−/− mice.

Injury-induced transforming growth factor β1 increases sphingosine 1-phosphate (S1P) generation by upregulating in sphingosine kinase 1 activity. The high levels of S1P formation stimulate the S1PR3-linked signaling pathway, which in turn increases vascular endothelial growth factor-A expression levels and angiogenesis in mouse corneas.

An increase in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in focal segmental glomerulosclerosis (FSGS). YAP inhibition by verteporfin induces nuclear exclusion of YAP, thus increasing the podocyte apoptosis and accelerating disease progression. Therefore, this study suggests that YAP activation and nuclear distribution in podocytes is an endogenous anti-apoptotic mechanism during the progression of FSGS.