{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:10:51Z","timestamp":1773004251908,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":274,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100019446","name":"Medical and Health Science and Technology Development Project of Shandong Province","doi-asserted-by":"publisher","award":["202407021041"],"award-info":[{"award-number":["202407021041"]}],"id":[{"id":"10.13039\/501100019446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR), a microvascular disease, also involves retinal neurodegeneration. M\u00fcller cells exert an important role in the retina, and their destabilization and reduction affect the physiological function of the retina. To investigate the effect and mechanism of hedgehog acyltransferase\u2010like (Hhatl) on M\u00fcller cells in DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The differentially expressed genes (DEGs) in M\u00fcller cells of DR rats were first analyzed by single\u2010cell transcriptomics techniques (scRNA\u2010seq). Regulating Hhatl expression, cell viability was detected using cell counting kit\u20108 (CCK\u20108) assay; apoptosis was detected by terminal deoxynucleotidyl transferase nick\u2010end labeling (TUNEL); the expression of B\u2010cell lymphoma 2 (Bcl2), Bcl2\u2010associated X protein (Bax), activating transcription factor 6 (ATF6), C\/EBP homologous protein (CHOP), and glucose\u2010regulated protein 78 (GRP78) was assessed by immunofluorescence; and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentration was determined by fluorescence quantification to observe the effect and mechanism of Hhatl on M\u00fcller cells of the high glucose (HG)\u2010treated rats. Finally, the results of the cell assays were verified in male 6\u2010week\u2010old Zucker (fa\/fa) diabetic fatty (ZDF) rats. Viral vectors expressing Hhatl were injected into the vitreous of ZDF rats, and apoptosis and endoplasmic reticulum stress (ERS)\u2010related indices in rat retinal cells were detected using immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA\u2010seq analysis revealed that Hhatl was low\u2010expressed in M\u00fcller cells of DR rats. In vitro assays confirmed that upregulation of Hhatl could increase rMC\u20101 Bcl2 expression, decrease Bax expression, and reduce apoptosis in HG environments. In addition, Hhatl did downregulate ATF6 expression, decrease CHOP and GRP78 levels, and reduce Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentration. Animal assays showed that Hhatl overexpression in the vitreous of ZDF rats did elevate Bcl2 level, decrease Bax expression, and reduce ATF6, CHOP, and GRP78 levels, which alleviated ERS in the retina of ZDF rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\u200b Hhatl reduces apoptosis of M\u00fcller cells in DR by alleviating ATF6\u2010related ERS signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ije\/6615457","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T06:04:12Z","timestamp":1759471452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hhatl Reduces Apoptosis of M\u00fcller Cells in Diabetic Retinopathy by Relieving Endoplasmic Reticulum 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