Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by T
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Chinese Medicine Open Access
RESEARCH
Micronized sacchachitin promotes satellite cell proliferation through TAK1‑JNK‑AP‑1 signaling pathway predominantly by TLR2 activation Meng‑Huang Wu1,2, Chuang‑Yu Lin3, Chun‑Yin Hou4, Ming‑Thau Sheu5*† and Hsi Chang6,7*†
Abstract Background: Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods: The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cul‑ tivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors. Results: Our data revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC prolifera‑ tion. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. Conclusion: Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration. Keywords: Sacchachitin, Satellite cells, TAK1-JNK-AP-1 signaling pathway, MAPK signal pathway, Muscle regeneration Background Ganoderma tsugae (GT) is a representative of Ganoderma sp., the traditional medicinal mushrooms that comprise of over 80 species. The history of Ganoderma *Correspondence: [email protected]; [email protected] † Ming-Thau Sheu and Hsi Chang contributed equally to this study 5 School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wuxing St., Taipei 11031, Taiwan 7 Department of Pediatrics, Taipei Medical University Hospital, No. 252 Wuxing St., Taipei 11031, Taiwan Full list of author information is available at the end of the article
sp. could be traced back to more than 2000 years [1], and it has been used for promoting health and extending life in China, Japan, and other East Asian countries. Investigation of this traditional medicinal mushroom by using modern scientific technology revealed that GT contains more than 400 bioactive substances, including sterols, steroids, fatty acids, polysaccharides, triterpenoids, nucleotides, proteins or peptides, and trace elements. Of these, the polysaccharides (PSs) were identified as the major source for biological activity and therapeutic use [2–4]. PSs possess antitum
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