Abstract
As transforming growth factor (TGF)-β inducible early gene-1 is highly expressed in skeletal muscle, the effect of TIEG1 gene deletion on the passive mechanical properties of slow and fast twitch muscle fibers was analyzed. Twenty five muscle fibers were harvested from soleus (Sol) and extensor digitorum longus (EDL) muscles from TIEG1-/- (N = 5) and control (N = 5) mice. Mechanical tests were performed on fibers and the dynamic and static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data. In parallel, immunohistochemical analyses were performed on three serial transverse sections to detect the myosin isoforms within the slow and fast muscles. The percentage and the mean cross sectional area of each fiber type were calculated. These tests revealed a significant increase in the mechanical stress properties for the TIEG1-/- Sol fibers while a significant decrease appeared for the TIEG1-/- EDL fibers. Hill model tracked the shape of the experimental relaxation curve for both genotypes and both fiber types. Immunohistochemical results showed hypertrophy of all fiber types for TIEG1-/- muscles with an increase in the percentage of glycolytic fibers (IIX, and IIB) and a decrease of oxidative fibers (I, and IIA). This study has provided new insights into the role of TIEG1, known as KLF10, in the functional (SoltypeI: more resistant, EDLtypeIIB: less resistant) and morphological (glycolytic hypertrophy) properties of fast and slow twitch skeletal muscles. Further investigation at the cellular level will better reveal the role of the TIEG1 gene in skeletal muscle tissue.
Highlights
Transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) was originally identified as a primary response gene following TGF-β treatment of human osteoblasts [1]
Muscle fiber diameters for the Sol and extensor digitorum longus (EDL) TIEG1-/- fibers were significantly (P
The decrease in hysteresis was similar for both fiber types, ~ 10% Sol and ~ 20% EDL, while no significant differences were found between genotypes
Summary
Transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) was originally identified as a primary response gene following TGF-β treatment of human osteoblasts [1]. The TIEG1 mRNA is known to be induced within 30 minutes of growth factor treatment, with a maximum induction occurring by 90 minutes. Muscle Mechanical Properties of TIEG1 KO Mice. The expressed TIEG1 protein is very labile as it is targeted rapidly for proteosomal degradation by the E3 ubiquitin ligase, SIAH [2]. TIEG1 is expressed in a wide variety of tissues with maximal RNA expression being observed in skeletal muscle [1, 3,4,5,6,7]. TIEG1 is a key mediator of TGF-β signaling [8,9,10] and overexpression of TIEG1 in multiple cell types mimics TGF-β actions [5, 6, 11]
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