{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:47:18Z","timestamp":1785646038590,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019535","name":"Texas Tech University Health Sciences Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019535","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/052r2q311","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK134893"],"award-info":[{"award-number":["R01 DK134893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01 DK134893"],"award-info":[{"award-number":["R01 DK134893"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Diabetic painful neuropathy (DPN) is a common complication of diabetes. Despite ongoing efforts, the underlying biological mechanisms of DPN remain poorly understood. Hyperglycemia-mediated oxidative stress can affect cell barrier properties, triggering low-grade inflammation. Previous studies have reported increased histone deacetylase (HDAC) activity and altered expression of tight junction proteins in diabetes, which may link to nerve damage. This study examined the effects of the HDAC inhibitor FK228 on cell barrier-mediated changes in the spinal cord and dorsal root ganglia (DRG) of type 2 diabetic mice. Diabetic mice were treated with FK228 (1 mg\/kg, twice a week for 3 weeks). Behavioral assessment of cold hypersensitivity was assessed at the end of the treatment regimen. In vitro studies were conducted using ND7\/23 immortalized DRG cells. The expression of tight junction proteins (occludin, claudin-1, and zona occludens-1 or ZO-1) and a number of stress-related cellular markers, including HDAC2, growth-associated protein (GAP) 43, epidermal growth factor receptor (EGFR), and nuclear factor erythroid 2-related factor (Nrf2), were evaluated in DRG, spinal cord tissue, and cultured ND7\/23 DRG cells following treatment. FK228 treatment demonstrated changes in cold pain sensitivity as well as the expression of tight junction proteins and stress related markers in both in vivo and in vitro models of diabetic neuropathy. These findings indicate that HDAC inhibition by FK228 may support the maintenance of tight junction protein expression and alter cellular stress responses in the spinal cord and DRG, suggesting a possible role of FK228 in mitigating DPN.<\/jats:p>","DOI":"10.3390\/biology15151257","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:46:41Z","timestamp":1785487601000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FK228-Mediated Restoration of Tight Junction Proteins in Diabetic Neuropathy"],"prefix":"10.3390","volume":"15","author":[{"given":"Eileen","family":"Chen","sequence":"first","affiliation":[{"name":"Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1754-762X","authenticated-orcid":false,"given":"Vikram","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9193-5190","authenticated-orcid":false,"given":"Erina","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amogh","family":"Misra","sequence":"additional","affiliation":[{"name":"Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6491-1777","authenticated-orcid":false,"given":"Carlos","family":"Valdez","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-718X","authenticated-orcid":false,"given":"Munmun","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"},{"name":"Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"},{"name":"Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, 130 Rick Francis Street, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1093\/qjmed\/91.11.733","article-title":"Diabetic peripheral neuropathy and quality of life","volume":"91","author":"Benbow","year":"1998","journal-title":"QJM Int. 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