miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function
BIOMEDICINES
Authors: Boerschel, Christin S.; Stejskalova, Anna; Schaefer, Sebastian D.; Kiesel, Ludwig; Goette, Martin
Abstract
Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates Rho-associated protein kinase 2 (ROCK2), cofilin 2 (CFL2), Ras-related C3 botulinum toxin substrate 1 (RAC1), neural Wiskott-Aldrich syndrome protein (WASL), and integrin alpha-V (ITGAV). qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation ofITGAVandWASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters, and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.
Age and Growth of the Shortfin Mako Shark in the Southern Indian Ocean
MARINE AND COASTAL FISHERIES
Authors: Liu, Kwang-Ming; Sibagariang, Rina D'rita; Joung, Shoou-Jeng; Wang, Shyh-Bin
Abstract
The Shortfin Mako Isurus oxyrinchus is one of the major shark bycatch species in the longline fishery for tuna Thunnus spp. in the Indian Ocean; however, its biological information is still little known. This study estimated the age and growth of Shortfin Makos in the southern Indian Ocean. In total, 178 specimens (72 females and 106 males) were opportunistically collected by the scientific observers onboard Taiwanese large-scale longline fishing vessels from February 2013 to September 2016 in the southern Indian Ocean. The relationship of gutted weight (GW; in kg) to curved fork length (CFL; in cm) for both sexes combined was estimated as GW = 0.00001 x CFL2.517 (n = 170, r(2) = 0.85). Growth band pairs (including translucent and opaque bands) were counted based on sectioned vertebral centra from the caudal peduncle region. The periodicity of band-pair deposition on vertebral centra was estimated to be 1 year, with opaque bands deposited around August based on edge analysis. On this basis, the maximum observed ages of females and males were 18 and 14 years, respectively. The von Bertalanffy growth function best fitted the observed sexes-combined length-at-age data, with growth parameter estimates as L-infinity = 267.6 cm CFL, k = 0.123/year, and t(0) = -2.487 years (n = 159). The growth model could be improved for future stock assessments by increasing the sample size, particularly on very small (neonates and small subadults) and very large female Shortfin Makos.