{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:03:50Z","timestamp":1790424230564,"version":"4.1.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Background\/Aims: Ankylosing spondylitis (AS) is an inflammatory and immune disease leading to disability. Autophagy has been identified as a potential player in understanding the pathogenesis of AS. Methods: MiRNA-199a-5p and autophagy-related gene expression were determined by qRT-PCR or Western blot. Cytokine production was determined using ELISA assays. Proliferation was determined by MTT assay. MiRNA-199a-5p and Ras homolog enriched in brain (Rheb) were upregulated or downregulated by overexpression of plasmid or siRNA transfection. Results: Expression of miRNA-199a-5p, and autophagy-related genes LC3, beclin1, and ATG5 was significantly decreased in T cells of AS patients. Serum concentrations of TNF-\u03b1, IL-17, and IL-23 were promoted in AS patients, compared to healthy controls. MiRNA-199a-5p expression levels also showed significant negative correlations with the Ankylosing Spondylitis Disease Activity Score (ASDAS) and modified Stoke Ankylosing Spon dylitis Spinal Score (mSASSS) of AS patients. In Jurkat T cells and T cells isolated from AS patients, miRNA-199a-5p overexpression promoted autophagy-related genes expression and decreased TNF-\u03b1, IL-17, and IL-23 levels, whereas inhibition of miRNA-199a-5p attenuated these effects. As a direct target of miRNA-199a-5p, Rheb inhibition led to a striking decrease in the phosphorylation of the mechanistic target of rapamycin (mTOR) and induced autophagy. Moreover, pcDNA3.1-Rheb effectively reduced the inhibiting effects of mTOR signaling caused by miRNA-199a-5p overexpression. All effects were offset by pretreating with rapamycin (an mTOR antagonist). Conclusions: AS patients with advanced spinal damage had decreased autophagy levels and that miRNA-199a-5p may induce autophagy and inhibit the pathogenesis of AS by modulating the mTOR signaling via direct targeting Rheb.<\/jats:p>","DOI":"10.1159\/000480211","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T11:22:49Z","timestamp":1503400969000},"page":"2481-2491","source":"Crossref","is-referenced-by-count":45,"title":["MicroRNA-199a-5p Induced Autophagy and Inhibits the Pathogenesis of Ankylosing Spondylitis by Modulating the mTOR Signaling via Directly Targeting Ras Homolog Enriched in Brain (Rheb)"],"prefix":"10.1159","volume":"42","author":[{"given":"Yahan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2017,8,22]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480211","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/480211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:52:21Z","timestamp":1745427141000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000480211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,10,17]]}},"URL":"https:\/\/doi.org\/10.1159\/000480211","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}