title: The induction of the collagen capsule synthesis by Trichinella spiralis is closely related to protease-activated receptor 2.
abstract: The muscle-stage larvae of the parasite Trichinella spiralis have the ability to survive within host muscle tissue by virtue of the formation a nurse cell-parasite complex, which is surrounded by collagen. The formation of the complex is initiated by excretory-secretory (ES) proteins produced by the parasite. To determine the mechanisms underlying collagen capsule formation, we investigated the expression levels of several types of collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) in muscle cells. Synthesis of type I, IV, and VI collagen, which are major constituents of the collagen capsule, significantly increased during T. spiralis infection. In addition, we found that expression of the protease-activated receptor 2 (PAR2) gene was significantly increased during this period. Expression levels of the collagen genes and TGF-βI, Smad2, and Smad3 were induced by ES proteins and a PAR2 agonist, whereas their enhanced expression levels were reduced by a PAR2 antagonist and serine protease inhibitors. To evaluate the involvement of PAR2 during T. spiralis infection in vivo, we infected wild-type and PAR2 knockout (KO) mice with T. spiralis. Expression levels of type I, IV, and VI collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) were also decreased in the PAR2 KO mice. Phosphorylation of Smad2/3, which was increased by T. spiralis infection, was significantly diminished in the PAR2 KO mice. In conclusion, ES proteins containing serine protease most likely activate collagen synthesis via PAR2 and TGF-βI signaling, and this event could influence collagen capsule formation.
authors.affiliation: Department of Parasitology School of Medicine, Pusan National University, and Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Yangsan, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Parasitology School of Medicine, Pusan National University, and Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Yangsan, Republic of Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Cho
authors.affiliation: Department of Parasitology School of Medicine, Pusan National University, and Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Yangsan, Republic of Korea.
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Kang
authors.affiliation: Department of Parasitology School of Medicine, Pusan National University, and Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Yangsan, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Department of Parasitology School of Medicine, Pusan National University, and Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Yangsan, Republic of Korea. Electronic address: hsyu@pusan.ac.kr.
authors.forename: Hak Sun
authors.initials: HS
authors.lastname: Yu
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000235:genetics*; D007814:Larva; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000469:parasitology; D010766:Phosphorylation / Q000235:genetics; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057057:Serine Proteases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000469:parasitology / Q000503:physiopathology*
chemical_list: D015801:Helminth Proteins; D044464:Receptor, PAR-2; D015842:Serine Proteinase Inhibitors; D003094:Collagen; D057057:Serine Proteases
keywords: Collagen capsule; Protease-activated receptor 2 (PAR2); TGF-βI; Trichinella spiralis