Abstract:Objective To study the effect of low-concentration paclitaxel (PTX) on transforming growth factor-β1 (TGF-β1)-induced collagen deposition outside rat pulmonary artery smooth muscle cells (PASMCs) and related mechanism. Methods Primary rat PASMCs were divided into a blank control group (n=3), a model group (n=3), and a drug intervention group (n=3). No treatment was given for the blank control group. The model group was treated with TGF-β1 with a final concentration of 10 ng/mL. The drug intervention group was treated with PTX with a final concentration of 100 nmol/L in addition to the treatment in the model group. MTT colorimetry was used to measure cell proliferation. Quantitative real-time PCR was used to measure the relative mRNA expression of collagen type I (COL-I) and collagen type Ⅲ (COL-Ⅲ). ELISA was used to measure the OD value of COL-I and COL-Ⅲ proteins. Western blot was used to measure the relative protein expression of COL-I, COL-Ⅲ, and the key proteins of the TGF-β1/Smad3 signaling pathway (Smad3 and p-Smad3). Results Compared with the blank control group, the model group had significant increases in proliferation ability, relative mRNA and protein expression of COL-I and COL-Ⅲ, and relative protein expression of p-Smad3 (P P P > 0.05). Conclusions Low-concentration PTX exerts a marked inhibitory effect on TGF-β1-induced collagen deposition outside PASMCs, possibly by regulating the phosphorylation of Smad3 protein.
LUO Yan,XIE Liang,LIU Han-Min et al. Effect of low-concentration paclitaxel on collagen deposition outside rat pulmonary artery smooth muscle cells and related mechanism[J]. CJCP, 2019, 21(9): 924-929.
Zhang D, Yang R, Wang S, et al. Paclitaxel:new uses for an old drug[J]. Drug Des Devel Ther, 2014, 8:279-284.
[7]
Zhou J, Zhong DW, Wang QW, et al. Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-beta/Smad activity[J]. World J Gastroenterol, 2010, 16(26):3330-3334.
[8]
Zhang D, Sun L, Xian W, et al. Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity[J]. Lab Invest, 2010, 90(3):436-447.
González JM, Briones AM, Starcher B, et al. Influence of elastin on rat small artery mechanical properties[J]. Exp Physiol, 2005, 90(4):463-468.
[14]
Dong J, Ma Q. Myofibroblasts and lung fibrosis induced by carbon nanotube exposure[J]. Part Fibre Toxicol, 2016, 13(1):60.
[15]
Ni J, Shi Y, Li L, et al. Cardioprotection against heart failure by Shenfu injection via TGF-β/Smads signaling pathway[J]. Evid Based Complement Alternal Med, 2017, 2017:7083016.
Turner E, Erwin M, Atigh M, et al. In vitro and in vivo assessment of keratose as a novel excipient of paclitaxel coated balloons[J]. Front Pharmacol, 2018, 9:808.
Zhang D, Sun L, Xian W, et al. Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity[J]. Lab Invest, 2010, 90(3):436-447.
[21]
Gong K, Xing D, Li P, et al. cGMP inhibits TGF-beta signaling by sequestering Smad3 with cytosolic beta2-tubulin in pulmonary artery smooth muscle cells[J]. Mol Endocrinol, 2011, 25(10):1794-1803.
[22]
Dong C, Li Z, Alvarez R Jr, et al. Microtubule binding to Smads may regulate TGF beta activity[J]. Mol Cell, 2000, 5(1):27-34.
Lei Z, Xuan X, Yang R, et al. Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling[J]. Drug Des Devel Ther, 2015, 9:2139-2148.
[27]
Zhou J, Zhong DW, Wang QW, et al. Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-beta/Smad activity[J]. World J Gastroenterol, 2010, 16(26):3330-3334.