Transcription Factors Sp1 and Sp4 Regulate TRPV1 Gene Expression in Rat Sensory Neurons

Chu, Catherine; Zavala, Kathryn; Fahimi, Atefeh; Lee, Jessica; Xue, Qinggang; Eilers, Helge; Schumacher, Mark

doi:10.1186/1744-8069-7-44

Cited by 37 publications

(39 citation statements)

References 61 publications

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“…Upregulation of UT TRPV1 may lead to hypersensitization of the UT to mechanical stimulation (upon bladder filling) and in turn play a role in augmented reflex transmission (hyper-reflexia), a common symptom of DBD. NGF is reported to increase TRPV1 mRNA expression, mediated in part by the transcription factor Sp1 (21), and may underlie our findings of parallels in expression of both genes in STZ-DM UT. Upregulation of TRPV1 in STZ-DM UT may serve as a cell "braking mechanism" on NGF-proliferative drive, preventing a transition in barrier repopulation/repair activity to one of tumorigenesis (42,51).…”

Section: J-l)supporting

confidence: 67%

Impact of diabetes mellitus on bladder uroepithelial cells

Hanna-Mitchell

Ruiz

Daneshgari

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female SpragueDawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregulation of the polyol pathway and glucose transport genes in DM UT. While superficial UT repopulation occurred by 20 wk DM, the phenotype was different, with significant upregulation of receptors associated with UT mechanosensation (transient receptor potential vanilloid subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3, purinergic receptors P2X2 and P2X3). Compromised barrier function and alterations in UT mechanosensitivity and cell signaling could contribute to bladder instability, hyperactivity, and altered bladder sensation by modulating activity of afferent nerve endings, which appose the urothelium. Our results show that DM impacts urothelial homeostasis and may contribute to the underlying mechanisms of DBD. streptozotocin; urothelium; barrier; sensory; diabetic bladder dysfunction IN THE UNITED STATES alone it is estimated that approximately 19 million individuals, comprising both men and women, suffer from diabetes mellitus (DM) (13). DM is characterized by defects in the secretion of the hormone insulin by the pancreas and/or insulin signaling (53), which causes a dysregulation of cellular glucose uptake. Glucose is a large hydrophilic molecule that depends on specific glucose transporter (GLUT) proteins, present on the cell membrane, for cellular entry (12). From the GLUT family (13 cloned to date), GLUT4 is regulated by insulin and controls glucose uptake by skeletal muscle [which accounts for ϳ40% of total body mass (70)], cardiac muscle, and adipose tissue (75). Thus Type 1 and 2 diabetics are unable to efficiently transport glucose from the blood into these tissue groups (66) resulting in a state of hyperglycemia. Consequently, glucose inundates cells that express insulinindependent glucose transporters (such as GLUT1). Chronic elevation in cytosolic glucose leads to metabolic abnormalities such as osmotic and oxidative stress, thought to be factors that contribute to tissue injury and dysfunction associated with long-term DM (15, 61).The urinary bladder is one of th...

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Section: J-l)supporting

confidence: 67%

Impact of diabetes mellitus on bladder uroepithelial cells

Hanna-Mitchell

Ruiz

Daneshgari

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…1 and 2). Although, the exact reason for the small amount of template in the IgG control is not known, such background is not unusual (14,15). Nevertheless, in all cases we see a significant -fold enrichment of the positive binding region for anti-SP1 as well as for anti-CREB antibodies over the IgG control when expressed as a ratio of bound sequence over input (Fig.…”

Section: Figurementioning

confidence: 71%

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Hewett

Shi

Gong

et al. 2016

Journal of Biological Chemistry

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Edited by Paul E. FraserBurgeoning evidence supports a role for cyclooxygenase metabolites in regulating membrane excitability in various forms of synaptic plasticity. Two cyclooxygenases, COX-1 and COX-2, catalyze the initial step in the metabolism of arachidonic acid to prostaglandins. COX-2 is generally considered inducible, but in glutamatergic neurons in some brain regions, including the cerebral cortex, it is constitutively expressed. However, the transcriptional mechanisms by which this occurs have not been elucidated. Here, we used quantitative PCR and also analyzed reporter gene expression in a mouse line carrying a construct consisting of a portion of the proximal promoter region of the mouse COX-2 gene upstream of luciferase cDNA to characterize COX-2 basal transcriptional regulation in cortical neurons. Extracts from the whole brain and from the cerebral cortex, hippocampus, and olfactory bulbs exhibited high luciferase activity. Moreover, constitutive COX-2 expression and luciferase activity were detected in cortical neurons, but not in cortical astrocytes, cultured from wild-type and transgenic mice, respectively. Constitutive COX-2 expression depended on spontaneous but not evoked excitatory synaptic activity and was shown to be N-methyl-D-aspartate receptor-dependent. Constitutive promoter activity was reduced in neurons transfected with a dominant-negative cAMP response element binding protein (CREB) and was eliminated by mutating the CRE-binding site on the COX-2 promoter. However, mutation of the stimulatory protein-1 (Sp1)-binding site resulted in an N-methyl-D-aspartate receptor-dependent enhancement of COX-2 promoter activity. Basal binding of the transcription factors CREB and Sp1 to the native neuronal COX-2 promoter was confirmed. In toto, our data suggest that spontaneous glutamatergic synaptic activity regulates constitutive neuronal COX-2 expression via Sp1 and CREB protein-dependent transcriptional mechanisms.The first committed reaction in the metabolism of arachidonic acid to prostaglandins and thromboxanes is catalyzed by two related heme-containing bis-oxygenases, cyclooxygenase (COX) 1 and 2. These enzymes share 90% similarity in amino acid sequence and exhibit nearly identical enzyme kinetics (1, 2). Both catalyze two separate reactions, the first metabolizing arachidonic acid to PGG 2 3 (cyclooxygenase reaction), an intermediate that is subsequently reduced in the second reaction to the product, PGH 2 (peroxidase reaction). PGH 2 is the substrate for various synthases that generate individual biologically active prostaglandins and thromboxanes, often in a cell typespecific manner (3). Although both metabolize arachidonic acid to PGH 2 , the transcriptional regulation of each isoform differs. The PTGS1 gene encoding COX-1 lacks a TATA box motif in its 5Ј promoter region and is generally constitutively active in cells (4, 5). In contrast, the promoter regulatory region of the PTGS2 gene encoding COX-2 is not typically active but can be strongly and rapidly induced under specific...

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“…Additionally, there have some reports indicating that TRPV1 of TRPV family is closely related with the pathogenesis of asthma (27)(28)(29)(30). The TRPV1 on the epithelial cells of human respiratory tract can be activated by negatively charged particulate matter (PM) of 2-10μm diameter, resulting in apoptosis of the epithelial cells on airway (31).…”

Section: Discussionmentioning

confidence: 99%