title: Paeoniae radix reduces PDGF-stimulated hepatic stellate cell migration.
abstract: Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver fibrosis. In chronic liver injury, HSCs undergo transdifferentiation to an activated myofibroblastic phenotype and migrate to injured areas in response to chemotactic factors, producing extracellular matrix proteins such as collagen type I to repair the damage as well as overexpression of α-smooth muscle actin (α-SMA). Paeoniae Radix, the root of Paeonia lactiflora Pall, was investigated for PDGF-BB-induced HSC chemotaxis. Rat HSCs and LX-2, a human HSC cell line, were used for the in vitro experiments. Cell migration was analyzed by wound-healing and transwell assays. An ELISA and a Sircol collagen assay kit were used to detect the expressions of α-SMA and of collagen, respectively. Phosphorylations of mitogen-activated protein kinases, including ERK 1/2, p38, and JNK, were evaluated with immunoblotting. Results indicated that PDGF-BB increased migration as well as α-SMA and collagen expression in HSCs. Paeoniae Radix extracts and its active components, paeonol and 1,2,3,4,6-penta- O-galloyl- β-D-glucose (PGG), inhibited PDGF-BB-induced HSC migration and α-SMA and collagen expressions in a concentration-dependent manner. The inhibitory effects were associated with downregulation of PDGF receptor- α, ERK, p38, and JNK activation. Both paeonol and PGG participate in HSC migration, but via differential mechanisms.
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jong-Jen
authors.initials: JJ
authors.lastname: Kuo
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Wang
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Lee
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D054338:Cell Transdifferentiation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D008297:Male; D029596:Paeonia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000098:Acetophenones; D000199:Actins; D000077214:Becaplermin; D003094:Collagen; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D020574:Proto-Oncogene Proteins c-sis; C541116:ACTA2 protein, human; C498862:Acta2 protein, rat; C013638:paeonol; C435084:pentagalloylglucose