naa a22 4500 510805744 CHVBK 20180411083417.0 cr unu---uuuuu 180411e20130501xx s 000 0 eng 10.1007/s12576-013-0251-1 doi (NATIONALLICENCE)springer-10.1007/s12576-013-0251-1 Hepatocyte growth factor inhibits TGF-β1-induced myofibroblast differentiation in tendon fibroblasts: role of AMPK signaling pathway [Elektronische Daten] [Qingbo Cui, Songbin Fu, Zhaozhu Li] The transforming growth factor-β1 (TGF-β1)-induced myofibroblastic differentiation in tendon fibroblasts was thought to be one of the most important features of scar fibrosis formation, which is associated with occurrence of re-rupture. Previously, we reported that hepatocyte growth factor (HGF) inhibited TGF-β1-induced myofibroblast differentiation and extracellular matrix deposition in the Achilles tendon of rats. Here, we investigated the potential molecular mechanisms underlying the inhibitory effect of HGF on TGF-β1-induced myofibroblast differentiation. We found that treatment with HGF (10, 20, and 40ng/ml) increased phosphorylation of adenosine monophosphate kinase (AMPK) and acetyl-CoA carboxylase (ACC) in tendon fibroblasts. Pharmacological inhibition of the AMPK signaling pathway using compound C, a specific blocker of AMPK signaling, remarkably attenuated the inhibitory effect of HGF on TGF-β1-induced myofibroblastic differentiation in tendon fibroblasts. Moreover, small interfering RNA (siRNA)-mediated knockdown of AMPKα1 subunit decreased the inhibitory effect of HGF on TGF-β1-induced myofibroblastic differentiation in tendon fibroblasts. Finally, overexpression of constitutively active AMPKα1, which led to constitutive activation of the AMPK signaling pathway in tendon fibroblasts, mimicked the inhibitory effect of HGF on the TGF-β1-induced myofibroblastic differentiation. Our study therefore suggests that HGF inhibits TGF-β1-induced myofibroblastic differentiation via an AMPK signaling pathway-dependent manner in tendon fibroblasts. The Physiological Society of Japan and Springer Japan, 2013 HGF nationallicence TGF-β1 nationallicence Myofibroblastic differentiation nationallicence AMPK nationallicence Cui Qingbo Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150081, Harbin, China aut Fu Songbin Laboratory of Medical Genetics, Harbin Medical University, Harbin, China aut Li Zhaozhu Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150081, Harbin, China aut The Journal of Physiological Sciences Springer Japan 63/3(2013-05-01), 163-170 1880-6546 63:3<163 2013 63 12576 https://doi.org/10.1007/s12576-013-0251-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12576-013-0251-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cui Qingbo Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150081, Harbin, China aut NATIONALLICENCE 700 1- Fu Songbin Laboratory of Medical Genetics, Harbin Medical University, Harbin, China aut NATIONALLICENCE 700 1- Li Zhaozhu Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150081, Harbin, China aut NATIONALLICENCE 773 0- The Journal of Physiological Sciences Springer Japan 63/3(2013-05-01), 163-170 1880-6546 63:3<163 2013 63 12576 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer