Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation

Chronic cystitis is characterized by the hyperplasia and fibrosis of the bladder wall as well as attenuated compliance of the bladder. To further unravel its underlying molecular mechanism, the role of NFκB-JMJD3 signaling pathway in cystitis induced bladder fibrosis was investigated. Jmjd3 and Col1/3 expression was detected in a cystitis mouse model that was developed by intraperitoneal injection of cyclophosphamide (CYP). Human bladder smooth muscle cells (hBSMCs) were stimulated in vitro with lipopolysaccharide (LPS), and the cell proliferation and collagen accumulation were detected using EdU, CCK8, flow cytometry, qPCR, western blotting and immunofluorescence assays. Furthermore, the effects of NFκB and JMJD3 on cell proliferation and collagen accumulation were investigated using its selective antagonists, JSH23 and GSK-J4, respectively. CYP induced cystitis significantly increased Jmjd3, Col1 and Col3 expression in the bladder muscle cells. Furthermore, LPS stimulation markedly activated NFκB signaling and elevated JMJD3 expression in hBSMCs, and the activation of NFκB-JMJD3 signaling significantly promoted cell proliferation and collagen accumulation by upregulating CCND1 and COL1/3 expression, respectively. Our study reveals the critical role of NFκB-JMJD3 signaling in cystitis induced bladder reconstruction by regulating hBSMC proliferation and extracellular matrix (ECM) deposition, and these findings provide an avenue for effective treatment of patients with cystitis.     

Morphological Characteristics and Gene Mapping of Purple Apiculus Formation in Rice

Plant Molecular Biology Reporter - Apiculus color of grain is an important trait which is used as a morphological marker in rice (Oryza sativa. L). In the present study, the purple apiculus mutant...     

Mechanical understanding of hunting waves generated by killer whales

The wave wash hunting employed by Orcinus orca, also known as killer whales, is unique in that the prey is hunted outside of the water by generating waves. To quantitatively analyze the specific mechanism of the wave wash, data were obtained using computational fluid dynamics (CFD), and wave theory was introduced as the theoretical background to clarify the mechanism. The relationships between the swimming characteristics and wave parameters are defined in this paper. The results obtained by numerical investigation revealed that the wavelength increased with the swimming speed. Additionally, the wave height increased as the swimming speed increased and the swimming depth became shallower, and subsequently converged to a maximum of 2.42 m. The success of hunting is determined by two wave parameters, which indicate the intensity of the wave wash: the wave height and force exerted on the prey. The metabolic rate and the drag force are considered to evaluate the efficiency of the locomotion, which varied according to the swimming speed (V) and swimming depth (d) of the whales. To generate hunting waves efficiently, the optimal ranges of V and d were estimated to be 3 ~ 5 m/s and 0.5 m ~ 1.1 m respectively.     

MicroRNA-424 regulates epithelial-mesenchymal transition of endometrial carcinoma by directly targeting insulin-like growth factor 1 receptor

Although numerous miRNAs are reported to contribute to the carcinogenesis of malignant tumor, the specific role of miR-424 in endometrial carcinoma is seldom reported. To explore the effect of miR-424 on epithelial-mesenchymal transition and its underlying mechanism, we detected miR-424 expression in endometrial carcinoma tissue and cells. We found that miR-424 was significantly downregulated in endometrial carcinoma tissues and cells, especially in HEC-1B cells. To perform the functional analysis, we transfected HEC-1B with miR-424-mi, miR-424-inh, mi-control, and inh-control, respectively. We found that overexpression of miR-424 significantly decreases cell proliferation and migration, accompanied with the increased E-cadherin/Vimentin expression and the transition of mesenchymal to epithelial cell phenotype. We identified that insulin-like growth factor-1 receptor (IGF-1R) was a potential target of miR-424 by computational analysis followed by luciferase reporter assays. Of note, we found that the downregulation of miR-424 in HEC-1B cells enhanced endogenous IGF-1R expression. Further mechanistic analysis revealed that forced expression of IGF-1R in miR-424-mim transfected cells remedied the weakened migration resulting from overexpression of IGF-1R. Taken together, the results of the current study demonstrated that miR-424 was a tumor suppressor for endometrial carcinoma and a favorable factor against tumor progression through targeting IGF-1R, thus providing a target for the treatment of endometrial carcinoma.