Time course of skeletal muscle repair and gene expression following acute hind limb ischemia in mice

Abstract

DNA microarrays were used to measure the time course of gene expression during skeletal muscle damage and regeneration in mice following femoral artery ligation (FAL). We found 1,289 known sequences were differentially expressed between the FAL and control groups. Gene expression peaked on day 3, and the functional cluster "inflammation" contained the greatest number of genes. Muscle function was depressed for 3 days postligation, but returned to normal by day 7. Decreased muscle function was accompanied by reduced expression of genes involved in mitochondrial energy production, muscle contraction, and calcium handling. The induction of MyoD on day 1 denoted the beginning of muscle regeneration and was followed by the reemergence of the embryonic forms of muscle contractile proteins, which peaked at day 7. Transcriptional analysis indicated that the ischemic skeletal muscle may transition through a functional adaptation stage with recovery of contractile force prior to full regeneration. Several members of the insulin-like growth factor axis were coordinately induced in a time frame consistent with their playing a role in the regenerative process.

Transient Increase of Cytokines in the Acute Ischemic Tissue is Beneficial to Cell-Based Therapeutic Angiogenesis

“…Although we did not quantitatively measure more factors, previous studies have confirmed the remarkable release of many cytokines in acute ischemic tissues. [15][16][17][18] Second, our in vitro study found that total tissue protein extracted from acute ischemic limbs increased the survival, adhesion, and migration of BMCs to a much greater extent than total tissue protein extracted from chronic ischemic or normal non-ischemic limbs. Although we do not know the precise mechanism, we speculate that it is because of increased expression of some beneficial factors among the total cytokines.…”

SOCS-3 Induces Myoblast Differentiation

“…SOCS-3 mRNA expression is increased during cardiotoxin-induced muscle regeneration in the tibalis anterior muscle, and SOCS-3 protein expression is elevated during early stages of plantaris muscle hypertrophy induced by the synergist ablation model. 2 In support of these findings Paoni et al (51) found that during ischemia-induced muscle regeneration there was a significant up-regulation of SOCS-3 mRNA expression as measured by microarray analysis. This suggests that in the whole animal the up-regulation of SOCS-3 expression in skeletal muscle may contribute to the myogenesis process during the recovery from muscle damage or increased loading of the muscle, and the up-regulation of SOCS-3 expression may be induced by IGF-I.…”

HIF modulation of Wnt signaling regulates skeletal myogenesisin vivo

“…To determine whether HIF1α regulates adult skeletal myogenesis, we employed the femoral artery ligation (FAL) model of PAD (Borselli et al, 2010;Paoni et al, 2002). In this model, hindlimb ischemia injures skeletal muscle.…”

“…In murine models of PAD (Paoni et al, 2002;Borselli et al, 2010), hindlimb ischemia leads to adult muscle injury and subjects these damaged fibers, as well as adjacent PAX7 + progenitors, to O 2 deprivation. Upon revascularization and restored perfusion, muscle fiber regeneration ensues.…”