{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:47:37Z","timestamp":1772189257773,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The purpose of the current investigation was to elucidate what kinds of responsible mechanisms induce elongation of the sclera in myopic eyes. To do this, two-dimensional (2D) cultures of human scleral stromal fibroblasts (HSSFs) obtained from eyes with two different axial length (AL) groups, &lt;26 mm (low AL group, n = 2) and &gt;27 mm (high AL group, n = 3), were subjected to (1) measurements of Seahorse mitochondrial and glycolytic indices to evaluate biological aspects and (2) analysis by RNA sequencing. Extracellular flux analysis revealed that metabolic indices related to mitochondrial and glycolytic functions were higher in the low AL group than in the high AL group, suggesting that metabolic activities of HSSF cells are different depending the degree of AL. Based upon RNA sequencing of these low and high AL groups, the bioinformatic analyses using gene ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) of differentially expressed genes (DEGs) identified that sterol regulatory element-binding transcription factor 2 (SREBF2) is both a possible upstream regulator and a causal network regulator. Furthermore, SREBF1, insulin-induced gene 1 (INSIG1), and insulin-like growth factor 1 (IGF1) were detected as upstream regulators, and protein tyrosine phosphatase receptor type O (PTPRO) was detected as a causal network regulator. Since those possible regulators were all pivotally involved in lipid metabolisms including fatty acid (FA), triglyceride (TG) and cholesterol (Chol) biosynthesis, the findings reported here indicate that FA, TG and Chol biosynthesis regulation may be responsible mechanisms inducing AL elongation via HSSF.<\/jats:p>","DOI":"10.3390\/ijms25010501","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T11:19:21Z","timestamp":1703848761000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lipid Metabolism Regulators Are the Possible Determinant for Characteristics of Myopic Human Scleral Stroma Fibroblasts (HSSFs)"],"prefix":"10.3390","volume":"25","author":[{"given":"Hiroshi","family":"Ohguro","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Araya","family":"Umetsu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-1772","authenticated-orcid":false,"given":"Tatsuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Renal and Metabolic Medicine, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"},{"name":"Department of Cellular Physiology and Signal Transduction, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-3541","authenticated-orcid":false,"given":"Masato","family":"Furuhashi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Renal and Metabolic Medicine, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6532","authenticated-orcid":false,"given":"Megumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1136\/bjophthalmol-2017-311266","article-title":"Global prevalence of visual impairment associated with myopic macular degeneration and temporal trends from 2000 through 2050: Systematic review, meta-analysis and modelling","volume":"102","author":"Fricke","year":"2018","journal-title":"Br. 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