Wang Yunqian, Xue Lei, Li Huicong, Shi Jun, Chen Baoping
Department of Nephrology, Huaihe Hospital of Henan University No. 8 of Baobei Road Kaifeng 475000 Henan Province P. R. China
Department of Endocrinology, Huaihe Hospital of Henan University Kaifeng 475000 Henan Province P. R. China.
RSC Adv. 2019 Jan 14;9(3):1741-1746. doi: 10.1039/c8ra10547b. eCollection 2019 Jan 9.
Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications. However, the role of FOXO6 in diabetic nephropathy (DN) has not been fully understood. In the present study, we evaluated the functions of FOXO6 in high glucose (HG)-induced glomerular mesangial cells (MCs). The results showed that FOXO6 expression was significantly elevated in MCs after HG stimulation. Knockdown of FOXO6 by transfection with small interfering RNA (siRNA) targeting FOXO6 (siRNA-FOXO6) suppressed cell proliferation in MCs. The productions of extracellular matrix (ECM) components including collagen IV (Col IV) and fibronectin (FN) were markedly decreased after FOXO6 knockdown in MCs. Furthermore, knockdown of FOXO6 inhibited HG-induced activation of p38 MAPK signaling pathway in MCs. Collectively, these findings suggested that knockdown of FOXO6 inhibited cell proliferation and ECM accumulation in HG-induced MCs inhibiting p38 MAPK signaling pathway. FOXO6 might be a beneficial therapeutic target for the prevention and treatment of DN.
叉头框O6（FOXO6）是一种FOX转录因子，已被发现与糖尿病及其相关并发症有关。然而，FOXO6在糖尿病肾病（DN）中的作用尚未完全明确。在本研究中，我们评估了FOXO6在高糖（HG）诱导的肾小球系膜细胞（MCs）中的功能。结果显示，HG刺激后MCs中FOXO6的表达显著升高。通过转染靶向FOXO6的小干扰RNA（siRNA）（siRNA-FOXO6）敲低FOXO6可抑制MCs的细胞增殖。在MCs中敲低FOXO6后，包括IV型胶原（Col IV）和纤连蛋白（FN）在内的细胞外基质（ECM）成分的产生明显减少。此外，敲低FOXO6可抑制HG诱导的MCs中p38丝裂原活化蛋白激酶（MAPK）信号通路的激活。总的来说，这些发现表明，敲低FOXO6可抑制HG诱导的MCs中的细胞增殖和ECM积累，其机制可能与抑制p38 MAPK信号通路有关。FOXO6可能是预防和治疗DN的一个有益的治疗靶点。
