Zhang Ting, Li Xiaowen, Li Yu, Wang Hua
Department of Pediatrics, West China Second University Hospital, Sichuan University Chengdu, P. R. China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University Chengdu, P. R. China.
Int J Clin Exp Pathol. 2019 Oct 1;12(10):3772-3781. eCollection 2019.
Transforming growth factor-beta (TGF-β) is ubiquitously expressed in various tissues and functions in pathologic processes, including hyperoxia. In the present study, we investigated the expression and functional role of TGF-β in brain tissue during hyperoxia-induced brain damage. Three days old neonatal rats were treated with hyperoxic conditions (80% O) for 7 days, followed by TGF-β, Smad, and MAPK detection by western blotting and immunohistochemical staining. The functional role of TGF-β was assessed by treating hyperoxic neonatal rats with neutralizing antibody against TGF-β and caffeine, followed by histological and myelin basic protein (MBP) staining. Our results demonstrated upregulation of TGF-β and activation of the Smad/MAPK signaling pathway in brain tissue of neonatal rats under hyperoxic conditions. Injection of neutralizing antibody against TGF-β efficiently blocked TGF-β expression, accompanied by inactivation of the Smad/MAPK signaling pathway. Further evidence confirmed the attenuation of hyperoxia-induced brain damage by a neutralizing antibody against TGF-β in neonatal rats. Similar attenuation was also observed for caffeine. Collectively, our results indicate that TGF-β is a therapy target for hyperoxia-induced brain damage in neonates.
转化生长因子-β（TGF-β）在各种组织中广泛表达，并在包括高氧在内的病理过程中发挥作用。在本研究中，我们调查了TGF-β在高氧诱导脑损伤过程中脑组织中的表达及功能作用。对3日龄新生大鼠进行7天高氧条件（80%氧气）处理，随后通过蛋白质免疫印迹法和免疫组织化学染色检测TGF-β、Smad和丝裂原活化蛋白激酶（MAPK）。通过用抗TGF-β中和抗体和咖啡因处理高氧新生大鼠，然后进行组织学和髓鞘碱性蛋白（MBP）染色，评估TGF-β的功能作用。我们的结果表明，在高氧条件下新生大鼠脑组织中TGF-β上调，Smad/MAPK信号通路激活。注射抗TGF-β中和抗体可有效阻断TGF-β表达，并伴随Smad/MAPK信号通路失活。进一步的证据证实，抗TGF-β中和抗体可减轻新生大鼠高氧诱导的脑损伤。咖啡因也观察到类似的减轻作用。总体而言，我们的结果表明，TGF-β是新生儿高氧诱导脑损伤的治疗靶点。
