{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:25Z","timestamp":1760145865899,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C1084140-14","F23YY8109033"],"award-info":[{"award-number":["2019R1A2C1084140-14","F23YY8109033"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pusan National University","award":["2019R1A2C1084140-14","F23YY8109033"],"award-info":[{"award-number":["2019R1A2C1084140-14","F23YY8109033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.<\/jats:p>","DOI":"10.3390\/ijms25179530","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"9530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Role of the ALPI Gene Associated with Constipation Caused by Complement Component 3 Deficiency"],"prefix":"10.3390","volume":"25","author":[{"given":"Hee Jin","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Jeong","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayun","family":"Seol","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Ryeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Seo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9575","authenticated-orcid":false,"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Chungju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-5004","authenticated-orcid":false,"given":"Sun Il","family":"Choi","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-1725","authenticated-orcid":false,"given":"Dae Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19737","DOI":"10.1073\/pnas.0609791104","article-title":"Structural transitions of complement component C3 and its activation products","volume":"103","author":"Nishida","year":"2006","journal-title":"Proc. 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