{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:59:09Z","timestamp":1787025549216,"version":"build-2736575974"},"reference-count":19,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Personnel Cultivation Programme of Zhongda Hospital Southeast University","award":["CZXM-GSP-RC51"],"award-info":[{"award-number":["CZXM-GSP-RC51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: After spinal cord injury (SCI), pro-inflammatory microglia accumulate and impede axonal regeneration. We explored whether secreted protein acidic and rich in cysteine (Sparc) restrains microglial inflammation and fosters neurite outgrowth. Methods: Mouse microglial BV2 cells were polarized to a pro-inflammatory phenotype with lipopolysaccharides (LPSs). Sparc mRNA and protein were quantified by reverse transcription quantitative PCR (RT-qPCR). Sparc was overexpressed via plasmid transfection, then inflammatory cytokines, mitochondrial membrane potential (\u0394\u03c8m), reactive oxygen species (ROS), and oxidative-phosphorylation proteins, including voltage-dependent anion channel 1 (VDAC1), cytochrome c oxidase subunit 1 (COX1), and ATP synthase \u03b1 subunit (ATP5A), were assayed by Western blot, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Immunoprecipitation plus mass spectrometry, co-immunoprecipitation, and immunofluorescence confirmed the interaction between Sparc and ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52). Effects of Sparc overexpression alone or combined with Uba52 small interfering RNA (si-Uba52) were compared in LPS-induced BV2 cells. Finally, BV2 cells and a mouse hippocampal neuron (HT-22) were co-cultured in the Transwell chamber, and the changes in proliferation, apoptosis, and III-tubulin content of the latter were detected. Results: In LPS-induced BV2 cells, the tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), and ROS levels were elevated, while the IL-10 and transforming growth factor-\u03b2 (TGF-\u03b2) levels, \u0394\u03c8m, and the proteins levels of the VDAC1, COX1, ATP5A, and Sparc decreased. Sparc overexpression reversed these changes. Mechanistically, Sparc bound Uba52 and upregulated its expression; Uba52 knockdown abolished the anti-inflammatory and mitochondrial-protective effects of Sparc. In co-culture, Sparc overexpression rescued HT-22 neurons apoptosis and enhanced axonal growth, but the effects were also reversed by Uba52 knockdown. Conclusions: Sparc may maintain mitochondrial homeostasis by interacting with Uba52 to inhibit LPS-induced BV2 inflammatory response, thereby promoting neuronal axonal regeneration. This suggests that Sparc may play a potential role in SCI repair.<\/jats:p>","DOI":"10.31083\/fbl42005","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:46:16Z","timestamp":1756773976000},"source":"Crossref","is-referenced-by-count":2,"title":["Sparc Suppresses Microglial Neuroinflammation and Promotes Axonal Regeneration by Interacting With Uba52"],"prefix":"10.31083","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-0231","authenticated-orcid":true,"given":"Hangyu","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Zhongda Hospital Southeast University, 210009 Nanjing, Jiangsu, China"},{"name":"Medicine School, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Shanghai Sixth People\u2019s Hospital, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Hu","sequence":"first","affiliation":[{"name":"Medicine School, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefu","family":"Xu","sequence":"first","affiliation":[{"name":"Medicine School, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangkai","family":"Yu","sequence":"first","affiliation":[{"name":"Medicine School, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-1780","authenticated-orcid":true,"given":"Chengming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Zhongda Hospital Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Izzy S. 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