Regulatory Peptides最新文献

{"title":"Glucose-dependent insulinotropic polypeptide lowers branched chain amino acids in hyperglycemic rats","authors":"Peter Spégel ,&nbsp;Andreas Lindqvist ,&nbsp;Monica Sandberg ,&nbsp;Nils Wierup","doi":"10.1016/j.regpep.2013.12.009","DOIUrl":"10.1016/j.regpep.2013.12.009","url":null,"abstract":"<div><p><span><span>Hypersecretion of the incretin hormone<span> glucose-dependent insulinotropic polypeptide (GIP) has been associated with obesity and glucose intolerance. This condition has been suggested to be linked to GIP resistance. Besides its insulinotropic effect, GIP also directly affects </span></span>glucose uptake<span> and lipid metabolism. This notwithstanding, effects of GIP on other circulating metabolites than glucose have not been thoroughly investigated. Here, we examined effects of infusion of various concentrations of GIP in normo- and hyperglycemic rats on serum metabolite profiles. We found that, despite a decrease in serum glucose levels (−</span></span> <!-->26%, p<!--> <!-->&lt;<!--> <span>0.01), the serum metabolite profile was largely unaffected by GIP infusion in normoglycemic rats. Interestingly, levels of branched chain amino acids<span> and the ketone body β-hydroxybutyrate were decreased by 21% (p</span></span> <!-->&lt;<!--> <!-->0.05) and 27% (p<!--> <!-->&lt;<!--> <!-->0.001), respectively, in hyperglycemic rats infused with 60<!--> <!-->ng/ml GIP. Hence, our data suggest that GIP provokes a decrease in BCAA levels and ketone body production. Increased concentrations of these metabolites have been associated with obesity and T2D.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.12.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32020228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemodynamic regulator and mitogenic growth factor: Re-visiting the age old question with ACE2 and Jak2","authors":"Peter P. Sayeski","doi":"10.1016/j.regpep.2014.03.002","DOIUrl":"10.1016/j.regpep.2014.03.002","url":null,"abstract":"","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.03.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32177275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is association between thyroid hormones and gut peptides, ghrelin and obestatin, able to suggest new regulatory relation between the HPT axis and gut?","authors":"Ali Emami ,&nbsp;Reza Nazem,&nbsp;Mehdi Hedayati","doi":"10.1016/j.regpep.2014.01.001","DOIUrl":"10.1016/j.regpep.2014.01.001","url":null,"abstract":"<div><h3>Background</h3><p><span>Ghrelin and </span>obestatin<span> are important appetite- and energy-regulating peptides, secreted by the stomach. These gut peptides and thyroid hormones are involved in metabolism regulation<span>. Although subclinical thyroidism is common, to date, very few studies have been reported about gut hormones<span> in thyroid dysfunction, and their results are controversial. The purpose of this study was to investigate ghrelin and obestatin in patients with subclinical hypo- and hyperthyroidism. Moreover, is association between thyroid hormones and gut peptides able to suggest new regulatory relation between the HPT axis and gut?</span></span></span></p></div><div><h3>Materials and methods</h3><p><span>The study group included 70 subclinical hypo- and hyperthyroid subjects (in equal groups) and 35 healthy euthyroid controls. Serum values of ghrelin, obestatin, free T3, </span>free T4, thyroid-stimulating hormone and the ratio of ghrelin to obestatin were measured in all participants.</p></div><div><h3>Results</h3><p>Ghrelin and obestatin both decreased in subclinical hypothyroid subjects (320<!--> <!-->±<!--> <!-->81<!--> <!-->ng/l and 44.3<!--> <!-->±<!--> <!-->11.7<!--> <!-->ng/l, respectively) compared to the control group (487<!--> <!-->±<!--> <!-->110<!--> <!-->ng/l and 58.5<!--> <!-->±<!--> <!-->10.3<!--> <!-->ng/l, respectively). On the other hand, ghrelin and obestatin both increased in subclinical hyperthyroid subjects (750<!--> <!-->±<!--> <!-->289<!--> <!-->ng/l and 71.1<!--> <!-->±<!--> <!-->27.3<!--> <!-->ng/l, respectively) compared to the control group. In addition, ghrelin and obestatin showed strong correlations with TSH, FT3 and FT4.</p></div><div><h3>Conclusion</h3><p>This study shows that gut hormones are significantly associated with thyroid hormones. Thus, there may be a cross talk between the HPT axis and gut. We would like to consider new regulatory relation for description of the found data.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32099590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptide Y regulates the leptin receptors in rat hypothalamic and pituitary explant cultures","authors":"María Paula Di Yorio,&nbsp;María Guillermina Bilbao,&nbsp;Alicia Graciela Faletti","doi":"10.1016/j.regpep.2013.11.003","DOIUrl":"10.1016/j.regpep.2013.11.003","url":null,"abstract":"<div><p><span><span>The aim of this work was to investigate whether the expression of leptin receptors (OBR) in the hypothalamic–pituitary (HP) axis is regulated by the </span>orexigenic<span> neuropeptide Y<span> (NPY) during ovulation. To this end, we performed in vitro assays, using cultures of both hypothalamic and anterior pituitary<span> explants<span><span> from immature rats primed with gonadotropins to induce ovulation. In hypothalamic explants, </span>protein expression<span> of both the long and short OBR isoforms was increased by the presence of NPY at 100–500</span></span></span></span></span></span> <!-->ng/ml and at 300–500<!--> <!-->ng/ml, respectively. Similarly, in pituitary explants, protein expression of the long isoform was increased between 30 and 300<!--> <!-->ng/ml while that of the short isoform was increased only at 300<!--> <span>ng/ml. When both tissues were incubated with NPY and BIBP3226, a specific antagonist of the NPY Y1 receptor subtype, the NPY-induced protein expression was totally reversed by the antagonist at almost every concentration assayed. However, this antagonist was not always capable of blocking the increase caused by the presence of NPY at transcript level. In conclusion, our results indicate that NPY is able to regulate the expression of both the long and the short isoforms of OBR in the HP axis, at least in part, through the NPY Y1 receptor. These results reinforce the fact that NPY and its NPY Y1 receptor play a critical role in reproduction by modulating leptin sensitivity.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.11.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31915184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotropin-releasing factor-like peptide modifies the AMPA-, NMDA-dependent and GABAB-ergic properties of synaptic transmissions in vitro","authors":"Anatoly A. Mokrushin","doi":"10.1016/j.regpep.2013.11.001","DOIUrl":"10.1016/j.regpep.2013.11.001","url":null,"abstract":"<div><p><span>The aim of this study was to investigate the neurotrophic effects of the mystixin-7 mini-peptide (MTX, a synthetic corticotrophin-releasing-factor-like peptide-like peptide) using a slice-based system. The technique on-line monitoring of electrophysiological parameters (excitatory glutamatergic AMPAR-, NMDAR-dependent and inhibitory GABA</span>_B<span>-ergic postsynaptic mechanisms) in the olfactory cortex slices of the rat brain exposed to varied amounts of MTX was used. MTX in a dose-dependent manner inhibited both the AMPAR- and NMDAR-mediated postsynaptic processes. The peptide caused depression of inhibitory GABA</span>_B-ergic processes only at low doses of MTX (10, 25, 50<!--> <!-->mg/mL) while at higher doses (100, 250<!--> <!-->mg/mL) it enhanced them. These effects of MTX were reversible. AMPA-dependent (but not NMDA-mediated mechanisms) and inhibitory processes were restored after washing.</p><p><span>Triple reperfusion of slices with MTX (100</span> <!-->mg/mL) accelerated the inhibitory processes and induced NMDAR desensitization. MTX evoked the long-term depression on θ burst stimulation of the slices. This study did not only lead to the conclusion that the functions of the MTX mini-peptide is not limited to anti-inflammatory effects, but also is included modifications of excitatory glutamatergic AMPAR-, NMDAR-dependent and inhibitory GABA_B<span>-ergic postsynaptic mechanisms.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31902006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effect of anandamide on oxytocin and vasopressin secretion from neurohypophysis is mediated by nitric oxide","authors":"Valeria Luce ,&nbsp;Javier Fernandez Solari ,&nbsp;Valeria Rettori ,&nbsp;Andrea De Laurentiis","doi":"10.1016/j.regpep.2013.12.004","DOIUrl":"10.1016/j.regpep.2013.12.004","url":null,"abstract":"<div><p><span><span>The neurohypophyseal hormones<span> oxytocin (OT) and vasopressin (VP) are involved in behavioral, autonomic and neuroendocrine functions. Both peptides are synthesized in magnocellular neurons of paraventricular and </span></span>supraoptic nuclei<span> at hypothalamic level whose axons terminate in the neurohypophysis (NH), from where OT and VP are released into the systemic circulation. NH contains abundant nitric oxide (NO) synthase suggesting that </span></span>NO<span> plays a role in the release of these neuropeptides<span><span><span>. The endocannabinoid system<span> is present in magnocellular neurons of the hypothalamic neurohypophyseal system, and we have previously demonstrated that </span></span>endocannabinoids modulate </span>OT secretion at hypothalamic level.</span></span></p><p>In the present work, we investigated the <em>in vitro</em><span> effect of the endocannabinoid anandamide (AEA) on OT and VP release from NH of untreated adult male rats and the involvement of NO in this action.</span></p><p><span>Our results showed that AEA decreased OT and VP secretion from NH. AEA action was mediated by NO, since the inhibition of NO synthesis completely blocked this inhibitory effect. We found that cannabinoid receptor type 2 (CB</span>₂<span><span>) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are involved in the inhibitory effect of AEA because AM630 and </span>capsazepine, CB</span>₂<span> and TRPV1<span> antagonists respectively, but not AM251, a CB</span></span>₁ antagonist, blocked AEA effect at neurohypophyseal level.</p><p>These findings revealed an interaction between endocannabinoid, nitric oxide and oxytocin/vasopressin systems that could be involved in the modulation of homeostatic, behavioral and reproductive processes.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31959078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide-treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric exercise","authors":"Meng-Kwoon Sim ,&nbsp;Yong-Chiat Wong ,&nbsp;Xiao-Guang Xu ,&nbsp;Weng-Keong Loke","doi":"10.1016/j.regpep.2013.12.003","DOIUrl":"10.1016/j.regpep.2013.12.003","url":null,"abstract":"<div><p>L6 skeletal muscle cells overexpressed ICAM-1 when treated with H₂O₂. Maximum effect was observed at 200<!--> <!-->μM H₂O₂<span>. Des-aspartate-angiotensin I (DAA-I) concentration-dependently attenuated the overexpression. Maximum attenuation occurred at 10</span>^{−<!--> <!-->10} <!-->M DAA-I. H₂O₂ activated NFκB and its translocation into the nucleus of L6 muscle cells suggesting that NFκB mediates the H₂O₂-induced overexpression of ICAM-1. DAA-I inhibited the activation and translocation of NFκB. H₂O₂<span><span> is a major oxidant formed during skeletal muscle contraction and is implicated in </span>oxidative stress and skeletal muscle damage in excessive unaccustomed exercise. The data show that DAA-I has antioxidant action, and its action was further investigated in the soleus muscle of mice subjected to 240</span> <!-->min of eccentric exercise on a rodent treadmill. The eccentric exercise induced superoxide formation and overexpression of ICAM-1 in the soleus muscle of the mice at 3<!--> <!-->days post exercise. DAA-I (0.2<!--> <!-->nmole/kg/day) administered orally on day 1 (pre-exercise) and 2<!--> <span><span>days post-exercise attenuated both the ROS formation and ICAM-1 overexpression. Earlier studies show that DAA-I acts as an agonist on the </span>angiotensin AT</span>₁<span><span> receptor and elicits responses opposing those of angiotensin II. The present and earlier findings support the recent suggestion that angiotensin II is involved in skeletal muscle damage, and curtailment of its actions via </span>ACE inhibitors<span> and losartan protects and improves skeletal muscle damage. These findings open up new avenues for treatment and management of skeletal muscle damage via the interventions of the renin angiotensin system.</span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31950559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal rectal endocrine cells in patients with irritable bowel syndrome","authors":"Magdy El-Salhy ,&nbsp;Doris Gundersen ,&nbsp;Jan G. Hatlebakk ,&nbsp;Odd Helge Gilja ,&nbsp;Trygve Hausken","doi":"10.1016/j.regpep.2013.11.005","DOIUrl":"10.1016/j.regpep.2013.11.005","url":null,"abstract":"<div><p><span><span><span><span><span>Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a previous study the total number of </span>endocrine cells<span><span> in the rectum of IBS patients, as detected by chromogranin A, did not differ from that of healthy controls. While the total endocrine cell content of the rectum appears to be unchanged in IBS patients, changes in particular endocrine cells cannot be excluded. This study was undertaken, therefore, to investigate the cell density of different rectal endocrine cell types in (IBS) patients. Fifty patients with IBS (41 females and 9 males) were included in the study. Thirty patients had diarrhoea (IBS-D) and 20 had constipation (IBS-C) as the predominant symptom. Twenty-seven subjects were included as controls (19 females and 8 males). Rectal biopsy specimens were immunostained using the avidin–biotin-complex method for serotonin, </span>peptide YY (PYY), </span></span>pancreatic polypeptide (PP), and </span>oxyntomodulin and </span>somatostatin cells. The cell densities were quantified by computerised image analysis. The serotonin cell density did not differ significantly, although a type II statistical error cannot be excluded, due to the small size of the sample. The densities of PYY and Oxyntomodulin cells were significantly lower and that of somatostatin were significantly higher in IBS patients than controls. These abnormalities were observed in both IBS-D and IBS-C patients. The abnormalities in the endocrine cells observed in this study in the rectum differed considerably from those seen in the colon of IBS patients. This indicates that caution in using the rectum to represent the </span>large intestine<span> in these patients. These abnormalities could be primary (genetic) or secondary to changes in the gut hormones<span> found in other segments of the gut and/or other pathological processes. Although the-cause-and effect relationship of the abnormalities found in rectal endocrine cells is difficult to elucidate, they might contribute to the symptoms associated with IBS. The densities of PYY and somatostatin cells are potential biomarkers with good sensitivity and specificity for the diagnosis of IBS.</span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.11.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31936500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin A and B in vitro modify orexins receptors expression and Gonadotropins secretion of anterior pituitary cells of proestrous rats","authors":"N.I. Cataldi ,&nbsp;V.A.R. Lux Lantos ,&nbsp;C. Libertun","doi":"10.1016/j.regpep.2013.12.002","DOIUrl":"10.1016/j.regpep.2013.12.002","url":null,"abstract":"<div><h3>Aim</h3><p><span>Orexin<span> A and orexin B (hypocretins) are neuropeptides<span> synthesized mainly by neurons located in the lateral hypothalamus and projections throughout the brain. They are agonists at both the orexin 1 and orexin 2</span></span></span> <span>G protein-coupled receptors. They have been related to arousal, sleep and feeding, autonomic and neuroendocrine functions. Their role in the brain control of gonadotropins secretion was postulated in rodents and humans. Previously, we demonstrated the participation of the orexinergic system in attaining successful reproduction in </span><em>in vivo</em> studies.</p></div><div><h3>Methods</h3><p>We studied <em>in vitro</em><span><span> the effects of both neuropeptides, in the presence or absence of selective antagonists, on the mRNA expression of orexin 1 and orexin 2 receptors in anterior pituitary cells of proestrous rats, as well as the direct effects on FSH and </span>LH secretion.</span></p></div><div><h3>Results</h3><p><span>Both orexin A and orexin B increased FSH and LH secretion; these effects were suppressed by the orexin 1 receptor blocking agent SB-334867 and the orexin 2 </span>receptor antagonists JNJ-10397049. Orexin A and orexin B decreased OX1 receptor mRNA expression and this effect was modified only when both blocking agents were present. Neither orexin A nor the blocking drugs by themselves modified OX2 receptor mRNA expression. Orexin B treatment increased the mRNA expression of OX2 receptor. The effect was abolished only by the OX2 receptor antagonist.</p></div><div><h3>Conclusion</h3><p>In an <em>in vitro</em><span><span> model, we demonstrated a direct effect of orexins on gonadotropins release and orexins receptors expression, underlining the hypothesis that orexins participate in the brain control of </span>pituitary functions.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31950558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octreotide modulates the effects on fibrosis of TNF-α, TGF-β and PDGF in activated rat hepatic stellate cells","authors":"Stefanos Klironomos ,&nbsp;George Notas ,&nbsp;Ourania Sfakianaki ,&nbsp;Foteini Kiagiadaki ,&nbsp;Costas Xidakis ,&nbsp;Elias Kouroumalis","doi":"10.1016/j.regpep.2013.11.002","DOIUrl":"10.1016/j.regpep.2013.11.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Somatostatin<span> and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide<span> on cytokine activated hepatic stellate cells (HSC).</span></span></p></div><div><h3>Methods</h3><p><span><span><span><span>Primary HSCs were isolated from rats and were cultured on plastic for activation. Expression of somatostatin receptors (SSTR) was investigated in cultured HSCs by immunofluorescence and </span>western blot. The effect of octreotide on </span>cellular proliferation<span> was studied with the MTT assay<span> and western blot for α1-procollagen (α1-PROC) production in TNFα, TGF-β1 or PDGF treated HSCs. </span></span></span>Phosphotyrosine<span> (PTP) and phosphoserine–phosphothreonine (STP) phosphatases inhibition was performed with sodium orthovanadate and </span></span>okadaic acid respectively.</p></div><div><h3>Results</h3><p><span>Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their expression is enhanced by further HSC activation. Octreotide did not have an effect on HSC proliferation but inhibited plastic induced α1-PROC production. Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and TGFβ1 dependent expression of α1-PROC, while an opposite effect was observed in TNFα-induced cell proliferation and collagen production. </span>PTP inhibition reversed the inhibitory effect of octreotide on α1-PROC, but potentiated its effect on PDGF and TGFβ1 dependent α1-PROC production. Finally, STP inhibition profoundly inhibited α1-PROC expression in all cases suggesting that both STP and PTP phosphatases are important regulators of pro-fibrotic mechanisms.</p></div><div><h3>Conclusions</h3><p>The net effect of octreotide on HSCs and therefore liver fibrosis is subject to the cytokine microenvironment of these cells. This effect is modulated by PTPs and STPs inhibition. Especially in the case of STPs their profibrotic effects could be an interesting new therapeutic target in liver fibrosis.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2013.11.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31915808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}