文章标题:Inflammation-induced LncRNA SNHG1 orchestrates spermatogonium development in non-obstructive azoospermia via IL-17 A signaling pathway
作者列表:Yongtong Zhu, Maocai Li, Xiaomin Zhan, Li Liu, Cairong Chen, Yao Zhou, Pei He, Rui Hua
期刊:CELLULAR AND MOLECULAR LIFE SCIENCES
发表时间:2026-1-6
影响因子:6.2
DOI:10.1007/s00018-025-06055-3
主要研究成果:Abstract
Non-obstructive azoospermia (NOA) is a critical subtype of male infertility associated with inflammation. However, the molecular mechanisms underlying this phenomenon remain poorly understood. This study investigated the role of the inflammation-activated long non-coding RNA SNHG1 in NOA pathogenesis. Using lipopolysaccharide (LPS)-induced orchitis mouse models and spermatogonium cell lines (GC-1 spg and TCAM-2), we observed that both SNHG1 and the transcription factor SP1 were significantly upregulated, correlating with spermatogonium proliferation and loss of stemness. Mechanistically, SP1 directly binds to and transcriptionally activates the SNHG1 promoter, whereas SNHG1 knockdown rescued LPS-induced spermatogonium dysfunction without affecting SP1 expression. RNA-seq revealed that SNHG1 overexpression activated the IL-17 A signaling pathway. Notably, IL-17 A receptor blockade (Brodalumab) reversed the SNHG1-mediated proliferation arrest and stemness. Our findings demonstrated that the SP1-SNHG1-IL-17 A axis drives inflammatory spermatogenic failure, suggesting IL-17 A inhibition as a potential therapeutic direction.
