Disease relevance of REG3A

• Using siRNA directed against beta-catenin, we demonstrated that REG3A is a target of beta-catenin signaling in Huh7 hepatoma cells [1].
• Cloning and expression analysis of an ovine PAP-like protein cDNA, a gene differentially expressed in scrapie [2].
• Moreover, we also produced HIP/PAP protein by Escherichia coli cultures performed to generate specific antibodies [3].
• These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as biological marker of acute pancreatitis [4].
• Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis [4].

Psychiatry related information on REG3A

• The first is a 13-year-old Hispanic girl with severe RP, PAP, mental retardation and obesity (BMI >40) [5].
• Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking [6]?
• Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease [7].
• The measurement of transmural values allowed a reliable assessment of PAP changes occurring during apneas, and different degrees of such changes shown by different patients may be related to a host of factors relevant to wakefulness and sleep, including individual responsivity to hypoxic stimulus [8].
• This review presents the possible involvement of 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase in the etiology of bipolar disorder and the mechanism of action of Li [9].

High impact information on REG3A

• Both the proband and her affected brother had RP, PAP, mild mental retardation, morbid obesity (BMI >50 and 37, respectively), lobulated kidneys with prominent calyces and diabetes mellitus (diagnosed at ages 33 and 30, respectively) [5].
• Monospecific rabbit antiserums to PAPP-A, PAPP-C and hCS all stained the trophoblast cytoplasm equivalently in a continuous layer, usggesting that the same trophoblast cells synthesize all three pregnancy proteins [10].
• A review of the literature indicates that this is the second report of fatal pancreatitis associated with pentamidine therapy [11].
• Pancreatitis-associated arthritis. Sequential study of synovial fluid abnormalities [12].
• The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases [13].

Chemical compound and disease context of REG3A

• Using the PAP technique and the indirect immunofluorescence method, paraffin sections of formaldehyde fixed tissue specimens of 25 tumours (12 benign fibrous histiocytomas, 12 malignant fibrous histiocytomas, and 1 atypical fibroxanthoma) were studied [14].
• Acute pancreatitis associated with high-concentration lipid emulsion during total parenteral nutrition therapy for Crohn's disease [15].
• Pancreatitis associated with isotretinoin-induced hypertriglyceridemia [16].
• We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens [17].
• HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy [18].

Biological context of REG3A

• Comparisons of REG/PAP proteins between various species showed that the deduced amino acid sequences were conserved [2].
• A human pancreatic cDNA library was screened with the cDNA encoding rat "pancreatitis-associated protein" (PAP) [4].
• HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice [19].
• After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver [19].
• The human pancreatitis-associated protein (PAP)-encoding gene generates multiple transcripts through alternative use of 5' exons [20].

Anatomical context of REG3A

• In Northern blot analysis the expression of the ovine PAP-like protein mRNA was restricted to the ileal and jejunal Peyer's patches [2].
• PAP-like protein mRNA was detected in cells of the epithelial lining in most crypts and in some intestinal villi in the ileum and jejunum while in the colon and rectum, the PAP-like protein mRNA expression was only detected in the deep portion of a few crypts [2].
• Taken overall, these results suggest that HIP/PAP protein may be of potential importance to liver cell differentiation/proliferation [3].
• In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products [4].
• The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization [21].

Associations of REG3A with chemical compounds

• HIP/PAP increased hepatocyte DNA synthesis and protected hepatocytes against TNF-alpha plus actinomycin-D-induced apoptosis [22].
• Adenovirus-mediated pancreatitis associated protein I expression, however, reduced cell adhesion to laminin-1 and fibronectin with a loss of integrin participation [23].
• Our results suggest that PAP p37 is a single polypeptide compact and globular glycoprotein and is immunologically not related to the aforementioned proteins [24].
• Pancreatitis associated with ondansetron [25].
• Twenty-six patients with pancreatitis associated with alcohol ingestion received either glucagon or placebo in addition to intravenous fluids, nasogastric suction, and meperidine as needed [26].

Physical interactions of REG3A

• PDX-1 binds directly to the INGAP promoter as determined in electromobility shift and antibody supershift assays [27].

Regulatory relationships of REG3A

• Besides, PAP expressing HCCs had significantly frequent beta-catenin mutation, regardless of REG1A expression, P < 0.00001 [28].
• Importantly, directed migration and spreading on fibronectin of the responsive melanoma cells were also enhanced when purified rat pancreatitis associated protein I was added to the culture medium of noninfected cells [23].
• PDX-1 can repress stimulus-induced activation of the INGAP promoter [27].
• We also demonstrate for the first time that INGAP gene expression was significantly induced by treatment with interleukin (IL)-6 and further enhanced by a combination of IL-6 with dexamethazone and nicotinamide [29].
• These data suggest that PB treatment in SZ-injected diabetic hamsters partially restored beta-cell function through acting as an antioxidant and induced higher expression of Reg and INGAP genes in the pancreas of hamsters [30].

Other interactions of REG3A

• Consistent with this notion, the pancreatitis-associated mutation A16V in cationic trypsinogen increases the rate of chymotrypsin C-mediated processing of the activation peptide 4-fold and causes accelerated trypsinogen activation in vitro [31].
• Testing for pancreatitis-associated CFTR and PSTI genotypes may be useful in nonalcoholic pancreatitis [32].
• Remarkably, however, E79K trypsin activated anionic trypsinogen two-fold better than wild-type cationic trypsin did, while the common pancreatitis-associated mutants R122H or N29I had no such effect [33].
• On the other hand, the results clearly demonstrate that hereditary pancreatitis-associated mutations do not lead to increased or decreased trypsinogen activation by cathepsin B. Therefore, mutation-dependent alterations in cathepsin B-induced trypsinogen activation are not the cause of hereditary pancreatitis [34].
• Data from 89 random samples and 85 serial specimens from five women revealed that both PAPP-B and HPL (PAPP-D) disappeared within a day after delivery [35].

Analytical, diagnostic and therapeutic context of REG3A

• The cellular expression of the PAP-like protein mRNA in the ovine intestine was further characterized by in situ hybridization [2].
• Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis [4].
• Analysis by RT-PCR revealed the presence of at least three different types 5'-ends of human PAP/HIP transcripts which were derived from alternative use of 5'-exons [20].
• Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene [21].
• We demonstrated that HIP/PAP stimulated liver regeneration after partial hepatectomy [22].

References