Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Cell Commun Signal. 2024 May 6;22(1):257. doi: 10.1186/s12964-024-01644-4.
Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.
良性前列腺增生症（BPH）是一种多因素疾病，其中异常生长因子激活和胚胎再激活被认为是重要因素。在这里，我们证明转化生长因子β（TGF-β）/Rho 激酶 1（ROCK1）的异常激活通过招募间充质干细胞（MSCs）增加了 BPH 组织的干性，表明胚胎再激活在 BPH 中的重要作用。当 TGF-β/ROCK1 异常激活时，MSCs 被募集并分化为成纤维细胞/肌成纤维细胞，导致前列腺基质增生。进一步的研究表明，抑制 ROCK1 激活可抑制 MSC 迁移及其向基质分化的潜能。总之，我们的研究结果表明，TGF-β/ROCK1 的异常激活调节干细胞谱系特异性，小分子抑制剂 GSK269962A 可靶向 ROCK1，可能是 BPH 的一种潜在治疗方法。
