LSKL,InhibitorofThrombospondin(TSP-1)是一种四肽，源于潜在联系多肽，能够抑制TSP-1的活性，来降低TGF-β的活性，能够阻止肝损伤和肝纤维化。
LSKL, Inhibitor of Thrombospondin (TSP-1) is a peptide derived from the latency-associated peptide, inhibits thrombospondin (TSP-1) activation of TGF-β and prevents the progression of hepatic damage and fibrosis.
LSKL peptide is able to reduce liver fibrosis by inhibiting TGF-β activation[2].
LSKL (1 mg/kg, i.p.) can easily traverse the blood brain barrier. LSKL peptide also alleviates hydrocephalus and improves long-term cognitive function following SAH. Moreover, LSKL peptide inhibits subarachnoid fibrosis after SAH. LSKL treatment significantly decreases the activation of TGF-β1 in the CSF in comparison with that in the SAH+PBS group[1]. LSKL peptide (30 mg/kg, i.p.) successfully inhibits transforming growth factor (TGF) β-Smad signal activation induced by partial hepatectomy. LSKL peptide successfully attenuates TGF-β-Smad signal activation by antagonizing TSP-1, but not by reducing TSP-1 protein expression. LSKL peptide accelerates hepatocyte proliferation after hepatectomy[3].
[1]. Liao F, et al. LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting TSP1-mediated TGF-β1 signaling activity following subarachnoid hemorrhage in rats. Exp Ther Med. 2016 Oct;12(4):2537-2543. Epub 2016 Aug 31. [2]. Laurent MA, et al. In silico characterization of the interaction between LSKL peptide, a LAP-TGF-beta derived peptide, and ADAMTS1. Comput Biol Chem. 2016 Apr;61:155-61. [3]. Kuroki H, et al. Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor β signal activation and liver regeneration after hepatectomy in an experimental model. Br J Surg. 2015 Jun;102(7):813-25.
Animal experiment: | Wild-type 8–12-week-old male mice (C57BL/6) are used for all experiments. LSKL TSP-1 inhibitory peptide is diluted to 5 mg/mL with normal saline. In the LSKL peptide group, LSKL peptide (30 mg/kg bodyweight in 6 mL/kg) is administered intraperitoneally before abdominal wall closure and at 6 h after the 70 per cent hepatectomy. In the normal saline group, saline (6 mL/kg) is given intraperitoneally at the same time points. In the sham-operated group, laparotomy is performed and the incision is sutured after normal saline (6 mL/kg) have been administered intraperitoneally. |
参考文献: [1]. Liao F, et al. LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting TSP1-mediated TGF-β1 signaling activity following subarachnoid hemorrhage in rats. Exp Ther Med. 2016 Oct;12(4):2537-2543. Epub 2016 Aug 31. | |
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