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And the effect of s-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) in AP is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this research, AHCYL1 pancreatic acinar cell specific knockout (CKO) mice were constructed and AP was induced. The related mechanism was investigated in mice or primary cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>It was found that AHCYL1 was decreased in AP mice. CKO caused increased macrophage infiltration in AP pancreas. AHCYL1 binding to amino acid transporters decreased in AP. Amino acid uptake, mTOR inhibition, and MIF production were aggravated in AP with AHCYL1 deficiency. Differentially expressed PGK1 in proteomics was associated with both mTOR and MIF in the PPI network. PGK1 was found to be further increased in CKO AP pancreas, which was reversed by mTOR activator. MIF expression and secretion under AP were inhibited by mTOR activator or PGK1 inhibitor. MIF-induced macrophage migration could be reduced by mTOR activator or PGK1 inhibitor. N1-acetylspermine increased in the serum of CKO AP mice. CKO acinar cell culture under AP caused further increment in N1-acetylspermine production enzyme, SSAT, which was inhibited by mTOR activator or PGK1 inhibitor. MIF induced SSAT and cytokines from macrophages, and the latter was reduced by SSAT inhibitor. Finally, AHCYL1 binding to the deubiquitinase OTUD6B decreased in AP. OTUD6B knockdown caused AHCYL1 ubiquitination and its decrement. AHCYL1 recovery reduced cytokine release and macrophage infiltration in AP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The AHCYL1 deficiency\/amino acid uptake inhibition\/mTOR inhibition\/PGK1 up-regulation\/MIF secretion axis in acinar cells induced SSAT in macrophages and macrophage infiltration in the pancreas in AP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00535-026-02437-x","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T13:49:42Z","timestamp":1778334582000},"page":"1483-1501","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S-adenosylhomocysteine hydrolase-like protein 1 deficiency resulted in stronger inflammation reaction in acute pancreatitis"],"prefix":"10.1007","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-7649","authenticated-orcid":false,"given":"Juan","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-ao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Dai","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"issue":"7","key":"2437_CR1","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1053\/j.gastro.2019.01.268","volume":"156","author":"A Saluja","year":"2019","unstructured":"Saluja A, Dudeja V, Dawra R, Sah RP. 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