Inhibition of Human Corneal Myofibroblast Formation.
Inhibition of Human Corneal Myofibroblast Formation.
复制标题
DOI：
10.1167/iovs.18-24239
复制
发表时间：
2018-07-02
影响因子：
4.4
通讯作者：
Zieske JD
中科院分区：
文献类型：
--
作者：
Guo X;Sriram S;Tran JA;Hutcheon AEK;Zieske JD
Please try later.
Transforming growth factor-beta (TGF-β) isoform 1 (T1) is involved in corneal fibrotic wound healing by stimulating myofibroblast transformation and altering fibrotic gene expression. In this study, two specific inhibitors were used to dissect the relationship between myofibroblast generation and the TGF-β/Smad- or TGF-β/p38-signaling pathway in human corneal fibroblasts (HCF). In HCF, Trx-SARA (Smad-pathway inhibitor) was used to block the TGF-β/Smad-signaling pathway, and the p38 inhibitor (p38inh, SB202190) was used to inhibit p38MAPK, thus blocking the TGF-β/p38-signaling pathway. HCF ± Trx-SARA or Trx-GA (SARA control) were serum starved overnight in Eagle's minimum essential medium (EMEM) ± p38inh, grown in EMEM ± T1 ± p38inh for 24 hours, and then processed for indirect-immunofluorescence, Western blot, or quantitative real-time polymerase chain reaction to examine α-smooth muscle actin (αSMA) and other fibrotic genes, such as fibronectin, thrombospondin1, and type III collagen. In addition, the morphology and the effect of p38inh on myofibroblast phenotype after myofibroblast formation were examined. We observed that Trx-SARA had little effect on αSMA expression, indicating that blocking the Smad pathway did not significantly inhibit myofibroblast formation. However, p38inh did significantly inhibit αSMA and other fibrotic genes, thus efficiently preventing the transition of HCFs to myofibroblasts. In addition, morphology changed and αSMA decreased in myofibroblasts exposed to p38inh medium, as compared with controls. HCF transition to myofibroblasts was mainly through the p38 pathway. Therefore, blocking the p38 pathway may be a potential therapeutic tool for human corneal fibrosis prevention/treatment, because it controls myofibroblast formation in human corneal cells, while leaving other functions of T1 unaffected.
登录
查看更多内容
DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
3
作者：
Baum J;Duffy HS
通讯作者：
Duffy HS
影响因子：
--
作者：
Amiri F;Ghiyasvandian S;Navab E;Zakerimoghadam M
通讯作者：
Zakerimoghadam M
DOI：
10.1513/pats.201203-023aw
发表时间：
2012-07-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Fernandez, Isis E;Eickelberg, Oliver
通讯作者：
Eickelberg, Oliver
影响因子：
4.4
作者：
Guo, Xiaoqing;Hutcheon, Audrey E. K.;Ruberti, Jeffrey W.
通讯作者：
Ruberti, Jeffrey W.