Granulocyte Research Laboratory, Department of Haematology, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
Published: December 2011
AI Article Synopsis
Article Abstract
Smad4 is important in the TGF-β pathway and required for transcriptional activation and inhibition of cell growth after TGF-β1 stimulation. We demonstrate that miR-130a is differentially expressed during granulopoiesis and targets Smad4 mRNA. The transcript for Smad4 is present throughout neutrophil maturation, but Smad4 protein is undetectable in the most immature cells, where miR-130a is highly expressed. Two miR-130a binding sites were identified in the 3'-untranslated region of the Smad4 mRNA. Overexpression of miR-130a in HEK293, A549, and 32Dcl3 cells repressed synthesis of Smad4 protein without affecting Smad4 mRNA level. Repression of Smad4 synthesis in a granulocytic cell line by miR-130a reduced its sensitivity to TGF-β1-induced growth inhibition. This effect was reversed by inhibiting the activity of miR-130a with an antisense probe or by expressing a Smad4 mRNA lacking miR-130a binding sites. High endogenous miR-130a and Smad4 mRNA levels and low expression of Smad4 protein were found in the t(8;21)(q22;q22) acute myelogenous leukemia-derived cell line Kasumi-1. When miR-130a was inhibited by an antisense RNA, the amount of Smad4 protein increased in Kasumi-1 cells and rendered it susceptible for TGF-β1-mediated cell growth inhibition. Our data indicate that miR-130a is involved in cell cycle regulation of granulocytic cells through engagement of Smad4 in the TGF-β pathway.
The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.
Gingival overgrowth caused by cyclosporine A is due to increased fibroblast proliferation in gingival tissues. Cell cycle system balances proliferation and anti-proliferation of gingival fibroblasts and plays a role in the maintenance of its population in gingival tissues. When cells detect and respond to abnormalities (e.
To investigate the effect of Buzhong Yiqi Decoction on regulatory T cells(Treg) in experimental rats with autoimmune thyroiditis(EAT) through the transforming growth factor-β(TGF-β)/Smad signaling pathway. Female SD rats were immunized with iodine-rich drinking water combined with Freund's adjuvant and porcine thyroglobulin(pTG) to establish the EAT model of rats, and the levels of serum thyroperoxidase antibody(TPOAb) and thyroglobulin antibody(TGAb) were detected. Pathological sections by hematoxylin-eosin(HE) staining were observed.
Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Background: Helminth coinfection with tuberculosis (TB) can alter the phenotype and function of macrophages, which are the major host cells responsible for controlling (Mtb). However, it is not known whether helminth infection stimulates the release of host-derived extracellular vesicles (EVs) to induce or maintain their regulatory network that suppresses TB immunity. We previously showed that pre-exposure of human monocyte-derived macrophages (hMDMs) with protein antigens (ASC) results in reduced Mtb infection-driven proinflammation and gained bacterial control.
