Which to reduce extracellular matrix deposition and attenuate process of fibrosis. In a word, Smad2 and Smad3 could both be effective therapeutic approaches for improving skin wound healing and inhibiting progression of fibrotic conditions by interrupting the TGF-b signaling pathway. In this research, up-regulation of exogenous TLP in normal human skin fibroblasts was conducted in the current study and analyzed by Western Blot analysis, detecting that Terlipressin manufacturer phosphorylation levels of Smad3 decreased by 15 , though phosphorylation levels of Smad2, conversely, increased by up to 25 . And even the variation observed in p-Smad2 levels was much greater than that observed in p-Smad3 levels. However, Angelina’s finding reveals that without affecting the phosphorylation of Smad2 and Smad3, TLP may inhibit the formation of the Smad3/4 complex so as to specifically block the downstream pathway of Smad3 and to upregulate the Smad2 pathway. Based on this conclusion, it is logical that TLP blocks the Smad3 signaling pathway, thus suppressing the synthesis of Col I/III indirectly. However, the current experiment demonstrates opposite results, drawing doubt upon this conclusion. Based on the findings of the current study, it is more likely that TLP up-regulated the synthesis of collagens mainly through activation of Smad2, perhaps, with other signal pathways through cross-talks or due to the existence of a mutual regulator of many signaling pathways. This may be supported by the finding that the variation observed in p-Smad2 levels was much greater than that was observed in p-Smad3 levels caused by TLP treatment. Smad3 is required for many of the cellular responses to injury and disease pathogenesis, one of which is the Smad3 facilitation of KDM5A-IN-1 collagen synthesis. Because the upstream promoters of the 265 extracellular matrix genes have been confirmed to be induced by TGF-b/Smad3dependent signaling pathways, this hypothesis seems probable [33]. In addition, collagen synthesis has been demonstrated to be affected by many diverse factors. Hence, the action of TLP in these signaling pathways is not simply linear, which might be due to the existence of cross-talks with many other pathways or due to the existence of 
a mutual regulator of many signaling pathways. It is known that many regulators exist for collagen synthesis, such as type I collagen. Some relevant positive and negative regulatory proteins have also been identified that affect each pathway. To make the matter more complex, there also exist mutual influencesand competitions between different pathways that must be considered in living tissues. So far, the undergoing mechanism of TLP still need to further study. TLP represents a novel cytokine only recently discovered and characterize that may play a significant inhibitory role in the Smad3 pathway and activate other cytokines or signaling pathways for the promotion 1326631 of collagen synthesis. TLP facilitation of the fibrosis process, though indirect, is certainly significant. Although the specific mechanism of the TLP signaling pathway is currently unresolved and pending further investigation, the hypothesis that TLP may act as a regulator to balance the flux of Smad2 and Smad3 in TGF-b signaling and indirectly affect collagens synthesis is worthy of consideration. The specific mechanism of TLP’s regulating action remains unclear. In 2003, Angelina first reported that TLP can modulate the balance of the Smad2 and Smad3 signal reaction as an intermediate prote.Which to reduce extracellular matrix deposition and attenuate process of fibrosis. In a word, Smad2 and Smad3 could both be effective therapeutic approaches for improving skin wound healing and inhibiting progression of fibrotic conditions by interrupting the TGF-b signaling pathway. In this research, up-regulation of exogenous TLP in normal human skin fibroblasts was conducted in the current study and analyzed by Western Blot analysis, detecting that phosphorylation levels of Smad3 decreased by 15 , though phosphorylation levels of Smad2, conversely, increased by up to 25 . And even the variation observed in p-Smad2 levels was much greater than that observed in p-Smad3 levels. However, Angelina’s finding reveals that without affecting the phosphorylation of Smad2 and Smad3, TLP may inhibit the formation of the Smad3/4 complex so as to specifically block the downstream pathway of Smad3 and to upregulate the Smad2 pathway. Based on this conclusion, it is logical that TLP blocks the Smad3 signaling pathway, thus suppressing the synthesis of Col I/III indirectly. However, the current experiment demonstrates opposite results, drawing doubt upon this conclusion. Based on the findings of the current study, it is more likely that TLP up-regulated the synthesis of collagens mainly through activation of Smad2, perhaps, with other signal pathways through cross-talks or due to the existence of a mutual regulator of many signaling pathways. This may be supported by the finding that the variation observed in p-Smad2 levels was much greater than that was observed in p-Smad3 levels caused by TLP treatment. Smad3 is required for many of the cellular responses to injury and disease pathogenesis, one of which is the Smad3 facilitation of collagen synthesis. Because the upstream promoters of the 265 extracellular matrix genes have been confirmed to be induced by TGF-b/Smad3dependent signaling pathways, this hypothesis seems probable [33]. In addition, collagen synthesis has been demonstrated to be affected by many diverse factors. Hence, the action of TLP in these signaling pathways is not simply linear, which might be due to the existence of cross-talks with many other pathways or due to the existence of a mutual regulator of many signaling pathways. It is known that many regulators exist for collagen synthesis, such as type I collagen. Some relevant positive and negative regulatory proteins have also been identified that affect each pathway. To make the matter more complex, there also exist mutual influencesand competitions between different pathways that must be considered in living tissues. So far, the undergoing mechanism of TLP 
still need to further study. TLP represents a novel cytokine only recently discovered and characterize that may play a significant inhibitory role in the Smad3 pathway and activate other cytokines or signaling pathways for the promotion 1326631 of collagen synthesis. TLP facilitation of the fibrosis process, though indirect, is certainly significant. Although the specific mechanism of the TLP signaling pathway is currently unresolved and pending further investigation, the hypothesis that TLP may act as a regulator to balance the flux of Smad2 and Smad3 in TGF-b signaling and indirectly affect collagens synthesis is worthy of consideration. The specific mechanism of TLP’s regulating action remains unclear. In 2003, Angelina first reported that TLP can modulate the balance of the Smad2 and Smad3 signal reaction as an intermediate prote.
