Smad3 contributes to positioning of proliferating cells in colonic crypts by inducing EphB receptor protein expression

2011 ◽  
Vol 405 (4) ◽  
pp. 521-526 ◽  
Author(s):  
Kiyoshi Furukawa ◽  
Toru Sato ◽  
Tatsuro Katsuno ◽  
Tomoo Nakagawa ◽  
Yoshiko Noguchi ◽  
...  
2013 ◽  
Vol 79 (3) ◽  
pp. 169-178 ◽  
Author(s):  
Justin A. Indyk ◽  
Cristina Candido-Vitto ◽  
Irene M. Wolf ◽  
Shekhar Venkataraman ◽  
Ricardo Munoz ◽  
...  

2021 ◽  
pp. 096452842110392
Author(s):  
Yanting Yang ◽  
Dan Zhang ◽  
Lijie Wu ◽  
Ji Zhang ◽  
Danyan Wu ◽  
...  

Background: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear. Objective: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 were detected. Results: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1β and IL-18 decreased significantly in the Model + EA group (p < 0.01). Conclusion: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.


2000 ◽  
Vol 167 (1) ◽  
pp. 7-13 ◽  
Author(s):  
M Theodoropoulou ◽  
T Arzberger ◽  
Y Gruebler ◽  
Z Korali ◽  
P Mortini ◽  
...  

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.


2015 ◽  
Vol 100 (10) ◽  
pp. 1168-1176 ◽  
Author(s):  
Yuhei Makanae ◽  
Riki Ogasawara ◽  
Koji Sato ◽  
Yusuke Takamura ◽  
Kenji Matsutani ◽  
...  

2002 ◽  
Vol 3 (2) ◽  
pp. 97-108 ◽  
Author(s):  
Lisa M. Harrison-Bernard ◽  
John D. Imig ◽  
Pamela K. Carmines

Experiments were performed to evaluate the hypothesis that the early stage of Type 1 diabetes mellitus (DM) increases renal angiotensin II (AngII) concentration and angiotensin type 1 (AT1) receptor protein levels. Nineteen or twenty days after vehicle (Sham rats) or streptozotocin (STZ rats) treatment, plasma [AngII] was higher in STZ rats (152±23 fmol/ml) than in Sham rats (101±7 fmol/ml); however, kidney [AngII] did not differ between groups.AT1receptor protein expression was greater in STZ kidneys than in Sham kidneys. This increase was restricted to the cortex, whereAT1protein levels were elevated by 77±26% (42 kDa) and 101±16% (58 kDa) in STZ kidneys. Immunohistochemistry revealed this effect to be most evident in distal nephron segments including the connecting tubule/cortical collecting duct. Increased renal corticalAT1receptor protein and circulating AngII levels are consistent with an exaggerated AngII-dependent influence on renal function during the early stage of DM in the rat.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rikus Botha ◽  
Shree S Kumar ◽  
Natasha Grimsey ◽  
Emma I Kay ◽  
Kathleen Grace Mountjoy

Abstract The human melanocortin 4 receptor (hMC4R) plays a critical role in the regulation of energy balance with more than 150 distinct human obesity-associated mutations. Most exhibit defective MC4R functionality but six have been reported to associate with constitutive activity. This represents a conundrum since a lean phenotype is expected for enhanced MC4R signaling. Human melanocortin 2 receptor accessory protein alpha (hMRAPα) induces hMC4R constitutive activity in transfected HEK293 cells (1,2). We do not know whether the hMRAPα-induced gain-in-function for hMC4R would cause, or prevent, obesity because of this conundrum. Here, we hypothesize that wild-type hMC4R, obesity-associated constitutively active hMC4R and hMRAPα-induced constitutive active hMC4R can exist in distinct conformational states and elicit distinct signaling profiles. To test this, we compared transiently expressed HA-hMC4R in HEK293 cells for basal and agonist activation for adenylyl cyclase, Cre driven β-galactosidase reporter transcription, and receptor protein expression. Six previously reported obesity-associated hMC4R constitutively active variants were compared with two hMC4R constitutively active mutations not associated with obesity, two hMC4R variants associated with protection from development of obesity, five non-constitutively active hMC4R mutations associated with obesity, hMRAPα co-expressed with hMC4R, and wild-type hMC4R. Our data confirm hMC4R constitutive activity coupling to both adenylyl cyclase and Cre β-galactosidase reporter for only two hMC4R variants associated with obesity (H76R & L250Q), one hMC4R mutation (H158R) not associated with obesity, and hMRAPα co-expressed with hMC4R. We show α-MSH stimulated concentration curves for wild-type hMC4R, H76R, L250Q & H158R hMC4R variants and hMRAPα co-expressed with hMC4R coupling to adenylyl cyclase. Surprisingly, out of these, only wild-type hMC4R and H158R hMC4R variant exhibited α-MSH-stimulated Cre β-galactosidase reporter concentration curves. Western blotting and ELISA showed ~70% reduced cell surface and total receptor protein expression for hMC4R co-expressed with hMRAPα and obesity-associated constitutively active hMC4R variants, compared to wild-type hMC4R. To summarize, two constitutively active hMC4R variants (H76R and L250Q) associated with obesity, and hMC4R co-expressed with hMRAPα, share a signaling profile comprising protein expression and α-MSH stimulated functional coupling to adenylyl cyclase and Cre-reporter gene expression. We conclude (1) if hMC4R is co-expressed with hMRAPα in vivo it would likely contribute to human obesity, and (2) obesity-associated constitutively active hMC4R variants exhibit a signaling anomaly that may underpin development of anti-obesity therapeutics. 1. Kay EI, et al. J Mol Endocrinol. 2013;50:203-215. 2. Kay EI, et al. PLoS ONE. 2015;10(10):e0140320.


2010 ◽  
pp. no-no ◽  
Author(s):  
Noelle C. Anastasio ◽  
Maria Fe Lanfranco ◽  
Marcy J. Bubar ◽  
Patricia K. Seitz ◽  
Sonja J. Stutz ◽  
...  

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