Lin28b Overexpression Enhances Facial Nerve Regeneration and Functional Recovery Through AKT/mTOR Signaling Pathway Activation in Mice
Year: 2026
Type: article
Abstract: Background: Limited axonal regeneration in mature neurons hinders functional recovery after neural injury. This study aimed to investigate the conserved regulator Lin28, which governs pluripotency-to-differentiation transitions, and to elucidate its role and underlying mechanisms in post-injury neural repair within the facial motor nucleus. Methods: Using C57BL/6J wild-type mice, human Lin28b-inducible overexpression transgenic mice (iLIN28B), and reverse tetracycline-controlled transactivator (rtTA)-only transgenic controls, we established a facial nerve crush injury model (FNI). Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence were employed to systematically analyze Lin28's roles in facial nerve development and injury repair. Results: In wild-type mice, Lin28a/b were highly expressed in the facial nucleus during embryonic stages but significantly declined postnatally. On day 3 post-FNI, Lin28a/b expression was significantly upregulated while let-7a/b microRNAs were downregulated. In iLIN28B mice, Lin28b overexpression promoted facial motor functional recovery and axonal regeneration at 3 days post-FNI. Moreover, Lin28b overexpression significantly downregulated let-7 microRNA levels and enhanced phosphorylation of protein kinase B (Akt) at Ser473 (pAkt) and ribosomal protein S6 at Ser235/236 (pS6) in the facial nucleus. Conclusions: Collectively, these findings suggest that Lin28b promotes axonal regeneration following facial nerve injury by downregulating the let-7 microRNAs, while the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway mediates, at least in part, the pro-regenerative effect of Lin28b. This study identifies Lin28b as a novel regulator of facial nerve injury repair, highlighting its potential as a molecular therapeutic target for motor nerve regeneration.
Source: Discovery Medicine
Authors: Xiaoyan Guo, Qin Hu, Qi Lu, Kun Li, Shiming Yang, Weidong Shen
Institutions: Chinese PLA General Hospital, Xi'an Jiaotong University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7165143044
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