Increased colonic apelin production in rodents with experimental colitis and in humans with IBD

Han, Song; Wang, Guiyun; Qiu, Suimin; Motte, Carol A. de la; Wang, Hui Qun; Gómez, Guillermo A.; Englander, Ella W.; Greeley, George H.

doi:10.1016/j.regpep.2007.02.002

Cited by 61 publications

(49 citation statements)

References 42 publications

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“…Apelin was first isolated from stomach extracts, and studies on the actions of apelin in the gastrointestinal system have found functional, and possible cell survival, roles (Wang et al 2004, Susaki et al 2005, Han et al 2007). In the gastrointestinal system, apelin/APJ may be regulators of hormone (Wang et al 2004) and gastric acid (Ohno et al 2012) secretion.…”

Section: Other Functions Of the Apelinergic Systemmentioning

confidence: 99%

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

O’Carroll

Lolait

Harris

et al. 2013

Journal of Endocrinology

292

216

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The apelin receptor (APJ; gene symbol APLNR) is a member of the G protein-coupled receptor gene family. Neural gene expression patterns of APJ, and its cognate ligand apelin, in the brain implicate the apelinergic system in the regulation of a number of physiological processes. APJ and apelin are highly expressed in the hypothalamo-neurohypophysial system, which regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis, which controls the neuroendocrine response to stress, and in the forebrain and lower brainstem regions, which are involved in cardiovascular function. Recently, apelin, synthesised and secreted by adipocytes, has been described as a beneficial adipokine related to obesity, and there is growing awareness of a potential role for apelin and APJ in glucose and energy metabolism. In this review we provide a comprehensive overview of the structure, expression pattern and regulation of apelin and its receptor, as well as the main second messengers and signalling proteins activated by apelin. We also highlight the physiological and pathological roles that support this system as a novel therapeutic target for pharmacological intervention in treating conditions related to altered water balance, stress-induced disorders such as anxiety and depression, and cardiovascular and metabolic disorders.

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Section: Other Functions Of the Apelinergic Systemmentioning

confidence: 99%

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

O’Carroll

Lolait

Harris

et al. 2013

Journal of Endocrinology

292

216

View full text Add to dashboard Cite

show abstract

“…For measurement of pancreatic apelin and APJ mRNA and 18S rRNA expression levels, total cellular RNA was extracted and purified from pancreatic homogenates according to published procedures (8,16,55). For measurement of apelin expression levels in cell lines, total cellular RNA was extracted and purified using RNAqueous kits.…”

Section: Real-time Rt-pcr Analysis Of Apelin Apj and 18s Rrna Exprementioning

confidence: 99%

“…Pancreatic collagen-1␣1 and collagen-4 mRNA levels and 18S rRNA levels were measured using previously described methods (8,9,16,55). Pancreatic collagen-4, IB␣, IB␤, and CTGF protein levels were measured by Western blot analysis (51,52).…”

Section: Rna Slot-blot and Western Blot Analysesmentioning

confidence: 99%

“…Apelin has an inhibitory activity against human immunodeficiency virus infection (3,58), reduces proinflammatory cytokine production in spleen cells (13), and, in the mouse cardiovascular system, lowers abdominal aortic aneurysm formation by reducing diseaseassociated vascular inflammation (23). Our laboratory (16) reported that intestinal apelin is involved in the inflammatory response of the intestine. Emerging data indicate a role for apelin in regulation of fibrosis in the kidney, heart, and liver (24,29,32,45).…”

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confidence: 98%

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Pancreatitis activates pancreatic apelin-APJ axis in mice

Han

Englander

Gómez

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin's activities. Supramaximal cerulein induction of AP or CP caused significant ( P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-κB activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin's inhibition of extracellular matrix production. The apelin-associated changes in NF-κB binding may be linked to apelin's regulation of pancreatic inflammatory and fibrosis responses during pancreatitis.

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“…Like other regulatory peptides, apelin exerts a broad range of activities affecting multiple organ systems, including effects on heart contractility and blood pressure (3, 5), appetite and drinking behavior (22, 36), immune response (20), gastric acid secretion (21), and insulin and cholecystokinin secretion (33, 41). In addition, apelin has been shown to affect cell motility, proliferation, and apoptosis (10,12,15,17,24,34,37,44,45).Our laboratory (10) has reported that apelin expression in the GI tract is activated by inflammation. In mice and rats with experimental colitis, intestinal apelin production is upregulated, and in humans with inflammatory bowel disease, apelin immunostaining is increased in the colonic epithelium (10).…”

mentioning

confidence: 99%

A possible role for hypoxia-induced apelin expression in enteric cell proliferation

Han

Wang

Xiang

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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A possible role for hypoxia-induced apelin expression in enteric cell proliferation. Am J Physiol Regul Integr Comp Physiol 294: R1832-R1839, 2008. First published March 26, 2008 doi:10.1152/ajpregu.00083.2008.-Apelin is the endogenous ligand for the APJ receptor, and apelin and APJ are expressed in the gastrointestinal (GI) tract. Intestinal inflammation increases intestinal hypoxia-inducible factor (HIF) and apelin expression. Hypoxia and inflammation are closely linked cellular insults. The purpose of these studies was to investigate the influence of hypoxia on enteric apelin expression. Exposure of rat pups to acute hypoxia increased hepatic, stomach-duodenal, and colonic apelin mRNA levels 10-, 2-, and 2-fold, respectively (P Ͻ 0.05 vs. controls). Hypoxia also increased colonic APJ mRNA levels, and apelin treatment during hypoxia exposure enhanced colonic APJ mRNA levels further. In vitro hypoxia also increased apelin and APJ mRNA levels. The hypoxia-induced elevation in apelin expression is most likely mediated by HIF, since HIF-activated apelin transcriptional activity is dependent on an intact, putative HIF binding site in the rat apelin promoter. Acute exposure of rat pups to hypoxia lowered gastric and colonic epithelial cell proliferation; hypoxia in combination with apelin treatment increased epithelial proliferation by 50%. In vitro apelin treatment of enteric cells exposed to hypoxia increased cell proliferation. Apelin treatment during normoxia was ineffective. Our studies imply that the elevation in apelin expression during hypoxia and inflammation in the GI tract functions in part to stimulate epithelial cell proliferation.inflammation; peptide; rat; gastrointestinal tract APELIN IS THE ENDOGENOUS LIGAND for a G protein-coupled receptor, the APJ receptor (1,4,14). Apelin and APJ are expressed widely in the body. They are produced in the brain, kidney, adipose tissue, lung, mammary gland, gastrointestinal (GI) tract, and cardiovascular system (9, 14, 18, 25-27, 35, 38, 39, 41). Like other regulatory peptides, apelin exerts a broad range of activities affecting multiple organ systems, including effects on heart contractility and blood pressure (3, 5), appetite and drinking behavior (22, 36), immune response (20), gastric acid secretion (21), and insulin and cholecystokinin secretion (33, 41). In addition, apelin has been shown to affect cell motility, proliferation, and apoptosis (10,12,15,17,24,34,37,44,45).Our laboratory (10) has reported that apelin expression in the GI tract is activated by inflammation. In mice and rats with experimental colitis, intestinal apelin production is upregulated, and in humans with inflammatory bowel disease, apelin immunostaining is increased in the colonic epithelium (10). In addition, in rodents, lipopolysaccharide (LPS) administration increases intestinal apelin expression levels (Greeley GH, unpublished data). Inflammation and hypoxia are closely associated insults during cellular stress and may exert their influences by activation of common signaling pathwa...

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Increased colonic apelin production in rodents with experimental colitis and in humans with IBD

Cited by 61 publications

References 42 publications

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

Pancreatitis activates pancreatic apelin-APJ axis in mice

A possible role for hypoxia-induced apelin expression in enteric cell proliferation

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