The mechanism(s) by which Smads mediate and modulate the transforming growth factor (TGF)-b signal transduction pathway in fibrogenesis are not well characterized. We previously showed that Smad3 promotes a2(I) collagen gene (COL1A2) activation in human glomerular mesangial cells, potentially contributing to glomerulosclerosis. Here, we report that Sp1 binding is necessary for TGF-b1-induced ty...

Synphilin-1 is a cytoplasmic protein that has been shown to be involved in the control of energy balance. Previously, we reported on the generation of a human synphilin-1 transgenic mouse model (SP1), in which overexpression of human synphilin-1 resulted in hyperphagia and obesity. Here, behavioral measures in SP1 mice were compared with those of their age-matched controls (NTg) at two time poi...

Rabbit corneal epithelial cells cultured in the presence of 3T3 feeder cells undergo biochemical differentiation, as evidenced by their initial expression of K5 and K14 keratins characteristic of basal keratinocytes, followed by the subsequent expression of K3 and K12 keratin markers of corneal epithelial differentiation. Previous data established that mutations of an Sp1 site in a DNA element,...

BACKGROUND The capsaicin receptor, transient receptor potential vanilloid type -1 (TRPV1) directs complex roles in signal transduction including the detection of noxious stimuli arising from cellular injury and inflammation. Under pathophysiologic conditions, TRPV1 mRNA and receptor protein expression are elevated in dorsal root ganglion (DRG) neurons for weeks to months and is associated with ...

Jonsson, A. 2015. The Impact of the Neuropeptide Substance P (SP) Fragment SP1-7 on Chronic Neuropathic Pain. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 198. 64 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9206-9. There is an unmet medical need for the efficient treatment of neuropathic pain, a condition that affects approximately 10% o...

The transcription factor specificity protein 1 (Sp1) plays a role in the development and progression of various types of human cancers, while cancer stem cells (CSCs) are important in cancer cell self-renewal, resistance to chemotherapy and metastatic potential. This study investigated the role of Sp1 in colon CSC growth and apoptosis. Colon CSCs were successfully enriched using special culture...

-The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis and restenosis. Although several studies have implicated the growth inhibitory protein p27(Kip1) (p27) in the control of myocyte growth and hypertrophy, little is known about the molecular mechanisms that regulate p27 expression in the cardiovascular system. In the present study, we de...

Sp1 activates the transcription of many cellular and viral genes, and histone deacetylase 1 (HDAC1) removes the acetyl group of nucleosomal core histones. Treatment of cells with the histone deacetylase 1 inhibitor, TSA, robustly activates the transcription of the Sp1-dependent promoters, suggesting the inhibition of Sp1 activity which is critical in the activation of transcription, by HDAC1. W...

Using flow channel, we report that the application of a laminar shear stress induced a transient increase of tissue factor (TF) procoagulant activity in human umbilical vein endothelial cells (HUVEC), which was accompanied by a rapid and transient induction of the TF mRNA in the HUVEC. Functional analysis of the 2.2 kb TF 5' promoter indicated that a GC-rich region containing three copies each ...

The stratified squamous epithelium is a model system in which to define molecular mechanisms underlying the switch from proliferation to differentiation. This can be achieved through the functional dissection of keratin gene promoters. Having previously established the importance of keratin 4 in maintaining the differentiated phenotype in corneal epithelial cells, we investigated the role of Sp...