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| 1 | NKX6.3 protects against gastric mucosal atrophy by downregulatingβ-amyloid production显示文摘BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2.CONCLUSION NKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells. | Jung Hwan Yoon Yeon Soo Lee Olga Kim Hassan Ashktorab Duane T Smoot Suk Woo Nam Won Sang Park | 2019 | World Journal of Gastroenterology2019，25，3： | 6 |
| 2 | A new signal adaptive approach to positive time- frequency distributions with suppressed interference terrns显示文摘 | Nickel R M Sang T H Williams W J | 1998 | ICASSP1998，，： | 1 |
| 3 | Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking显示文摘 | Plant AJ Watkins RE Gushulak B O'Rourke T Jones W Streeton J Sang D | 2002 | Epidemiol Infect2002，128，1： | 1 |
| 4 | Genome-wide association studies of 14 agronomic traits in rice landraces显示文摘 | HUANG X WEI X SANG T | 2010 | Nature Genetics2010，42，11： | 1 |
| 5 | The chemistry and biotransformation of tea constitu- ents 显示文摘 | Sang S M Joshua D L Ho C T | 2011 | Pharmacological Research2011，64，： | 1 |
| 6 | Chloroplast DNA phylogeny reticulate evolution and biogeography of Paeonia(Paeoniaceae) 显示文摘 | Sang T Crawford D Stuessy T | 1997 | American Journal of Botany1997，84，8： | 1 |
| 7 | Documentation of reticulate evolution in peonies (Peonia) using internal transcribed spacer sequences of nuclear ribosomal DNA:implications for biogeography and concerted evolution显示文摘 | Crawford DJ Stuessy TF 1995 | 1995 | Pro Nati Acad Sci1995，92，： | 1 |
| 8 | Clinical evaluation of a rapid immunochromatographic test for the diagnosis of dengue virus infection显示文摘 | Sang C T Hoon L S Cuzzubbo A | 1998 | Clinical and Laboratory Immunology1998，5，3： | 1 |
| 9 | 显示文摘 | Dong S S Sang T P Hoon S C | 1999 | Thin Solid Films1999，354，： | 1 |
| 10 | Phylogeny of rice genomes with emphasis on origins of allotetraploid species 显示文摘 | Ge S Sang T Lu B R | 1999 | PNAS1999，96，14： | 1 |
| 11 | Mechanism of the su- peroxide scavenging activity of neoandrographolide - a natural product from Andrographis paniculata nees 显示文摘 | Kamdem R E Sang S Ho C T | 2002 | J Agr Food Chem2002，50，： | 1 |
| 12 | Generating binary Bernoulli sequences based on a class of ven-symmetric chaotic maps显示文摘 | SANG T WANG R L YAN Y X | 2001 | IEEE Trans on Communications2001，4，49： | 1 |
| 13 | A variable aperture fracture network model for flow and transport in fractured rocks显示文摘 | Nordqvist A W T sang Y W Tsang C F | 1992 | Water Resources Research1992，28，6： | 1 |
| 14 | Phylogeny of rice genomes with emphasis on origins of allotetraploid species 显示文摘 | GE S SANG T LU B R | 1999 | Proc Natl Acad Sci USA1999，96，14： | 1 |
| 15 | Description of a new species and new records of Rhacophorus genus(Amphibia:Anura:Rhacop horidae)with a review of amphibians and reptiles diversity of Ghu Yang Sin National Park (Dac Lac Province,Vietnam)显示文摘 | Orlov N L Sang N N Cuc H T | 2008 | Russian Journal of Herpetology2008，15，1： | 1 |
| 16 | Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src,ERK,and Akt survival signaling in human colon cancer cells显示文摘 | Liao C H Sang S Ho C T | 2005 | J Cellular Biochem2005，96，1： | 1 |
| 17 | A plant caspase-like protease activated during the hypersensitive response显示文摘 | NINA V C SANG H K ELENA S T | 2004 | Plant Cell2004，16，： | 1 |
| 18 | Origins of polyploids:an example from peonies (Paeonia) and a model for angiosperms显示文摘 | SANG T PAN J ZHANG D M | 2004 | Biological Journal of the Linnean Society2004，82，： | 1 |
| 19 | Measures and Dimensions of Filial Piety inKorea 显示文摘 | Sang K T | 1995 | The Gerontologist1995，35，2： | 1 |
| 20 | Effect of Gd implantation on the structural and magnetic properties of GaN and A1N显示文摘 | Han Sang Youn Hite J Thaler G T | 2006 | Applied Physics Letters2006，88，04： | 1 |
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