title: Regeneration of injured skeletal muscle in heat shock transcription factor 1-null mice.
abstract: The purpose of this study was to investigate a role of heat shock transcription factor 1 (HSF1)-mediated stress response during regeneration of injured soleus muscle by using HSF1-null mice. Cardiotoxin (CTX) was injected into the left muscle of male HSF1-null and wild-type mice under anesthesia with intraperitoneal injection of pentobarbital sodium. Injection of physiological saline was also performed into the right muscle. Soleus muscles were dissected bilaterally 2 and 4 weeks after the injection. The relative weight and fiber cross-sectional area in CTX-injected muscles of HSF1-null, not of wild-type, mice were less than controls with injection of physiological saline 4 weeks after the injury, indicating a slower regeneration. Injury-related increase of Pax7-positive muscle satellite cells in HSF1-null mice was inhibited versus wild-type mice. HSF1-deficiency generally caused decreases in the basal expression levels of heat shock proteins (HSPs). But the mRNA expression levels of HSP25 and HSP90α in HSF1-null mice were enhanced in response to CTX-injection, compared with wild-type mice. Significant up-regulations of proinflammatory cytokines, such as interleukin (IL) -6, IL-1β, and tumor necrosis factor mRNAs, with greater magnitude than in wild-type mice were observed in HSF1-deficient mouse muscle. HSF1 and/or HSF1-mediated stress response may play a key role in the regenerating process of injured skeletal muscle. HSF1 deficiency may depress the regenerating process of injured skeletal muscle via the partial depression of increase in Pax7-positive satellite cells. HSF1-deficiency-associated partial depression of skeletal muscle regeneration might also be attributed to up-regulation of proinflammatory cytokines.
authors.affiliation: Department of Orthopaedic Surgery, St. Marianna University School of Medicine Kawasaki, Japan.
authors.forename: Sono
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koya
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohno
authors.forename: Ayumi
authors.initials: A
authors.lastname: Goto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ikuita
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Ohira
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Egawa
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Goto
keywords: Heat shock proteins; heat shock transcription factor 1; proinflammatory cytokines; skeletal muscle regeneration