TGF-β3 regulates adhesion formation through the JNK/c-Jun pathway during flexor tendon healing.
TGF-β3 regulates adhesion formation through the JNK/c-Jun pathway during flexor tendon healing.
复制标题
TGF-β3 在屈肌腱愈合过程中通过 JNK/c-Jun 通路调节粘连形成
DOI：
10.1186/s12891-021-04691-x
复制
发表时间：
2021-09-30
影响因子：
2.3
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Jiang K;Li Y;Xiang C;Xiong Y;Jia J
受伤的屈肌腱愈合能力差，容易造成肌腱粘连。会影响肌腱功能的恢复，这对于外科医生来说仍然是一项长期而艰巨的任务。近年来，转化生长因子β（TGF-β）被广泛认为在屈肌腱修复中发挥着重要作用。本工作旨在探讨TGF-β3对趾长屈肌（FDL）肌腱修复大鼠的抗粘连和抗炎作用。大鼠屈趾肌腱撕裂吻合模型在第3天至第8天不经治疗、载体或TGF-β3过表达腺病毒载体(ad-TGF-β3)局部递送至受伤肌腱区域。随后，TGF-β3、TGF-β1/2、Smad3、Smad7、JNK、磷酸化(p)-JNK、c-Jun和磷酸化的表达Western blot检测(p)-c-Jun，RT-qPCR检测Mmp9和Mmp2的表达，粘连形成检测检测关节活动度(ROM)和滑动阻力，生物力学检测肌腱愈合的机械强度，HE染色检测屈肌腱组织的病理变化，免疫组化染色检测III型胶原表达，ELISA检测血清中IL-6、TNF-α、COX2和IL-1β的水平。未处理的大鼠模型在第14天至第28天期间，TGF-β3和Smad7的表达水平较低，TGF-β1/2和Smad3的表达水平较高。此外，在ad-TGF-β3治疗下，TGF-β3和Smad7的表达、ROM以及屈肌腱的机械强度显着增加，而滑行阻力、炎性细胞因子的含量、与媒介物处理相比，p-JNK/JNK、p-c-Jun/c-Jun 的比率，以及 TGF-β1/2、Smad3、Mmp9 和 Mmp2 基因的表达。同时，TGF-β3表现出更好的病理恢复过程，没有明显的胶原纤维坏死或断裂。此外，TGF-β3 显示屈肌腱愈合组织中 III 型胶原蛋白的表达显着减少。这些发现表明，TGF-β3 通过调节粘连形成有效地防止屈肌腱损伤。
The injured flexor tendon has poor healing ability, which is easy to cause tendon adhesion. It can affect the recovery of tendon function, which is still a long-term and difficult task for surgeons. Transforming growth factor β (TGF-β) has been widely considered to play an important role in flexor tendon repair in recent years. This work was to investigate the anti-adhesion and anti-inflammatory effects of TGF-β3 on flexor digitorum longus (FDL) tendon repair rats. Anastomosis models of tendon laceration in the flexion toes of rats were delivered with no treatment, vehicle, or TGF-β3 -overexpressed adenovirus vector (ad-TGF-β3) locally to the injured tendon area from day 3 to 8. Subsequently, the expression of TGF-β3, TGF-β1/2, Smad3, Smad7, JNK, phosphorylation (p)-JNK, c-Jun, and phosphorylation (p)-c-Jun were detected by western blot, the expression of Mmp9 and Mmp2 by RT-qPCR, the Range of motion (ROM) and gliding resistance by adhesion formation testing, the mechanical strength of tendon healing by biomechanical testing, the pathologic changes of flexor tendon tissues by HE staining, the expression of collagen type III by immunohistochemical staining, and the levels of IL-6, TNF-α, COX2 and IL-1β in serum by ELISA, respectively. Rat models treated with no treatment showed a lower elevation of TGF-β3 and Smad7 expression, and a higher elevation of TGF-β1/2 and Smad3 expression, during day 14 to day 28. Besides, under the treatment of ad-TGF-β3, a significantly increase was reflected in the expression of TGF-β3 and Smad7, ROM, as well as mechanical strength of flexor tendon, whereas significantly reduction was shown in gliding resistance, the content of inflammatory cytokines, the ratio of p-JNK/JNK, p-c-Jun/c-Jun, as well as the expression of TGF-β1/2, Smad3, Mmp9, and Mmp2 genes, as compared to those from vehicle treatment. Meanwhile, TGF-β3 demonstrated a better pathologic recovery process with no obvious necrosis or fracture of collagen fibers. Besides, TGF-β3 revealed a significant reduction of collagen type-III expression in the flexor tendon healing tissues. These findings suggested that TGF-β3 effectively protected against flexor tendon injury via regulating adhesion formation.
登录
查看更多内容
影响因子：
2.6
作者：
Bullard, KM;Longaker, MT;Lorenz, HP
通讯作者：
Lorenz, HP
影响因子：
3.4
作者：
Jiang, Ke;Chun, Guo;Xiong, Yan
通讯作者：
Xiong, Yan
影响因子：
7.6
作者：
Kohama, K;Nonaka, K;Ohishi, M
通讯作者：
Ohishi, M
影响因子：
4.6
作者：
Shen, Hua;Jayaram, Rohith;Thomopoulos, Stavros
通讯作者：
Thomopoulos, Stavros
影响因子：
3.7
作者：
Loiselle AE;Frisch BJ;Wolenski M;Jacobson JA;Calvi LM;Schwarz EM;Awad HA;O'Keefe RJ
通讯作者：
O'Keefe RJ