title: Activation of nuclear factor-κB following muscle eccentric contractions in humans is localized primarily to skeletal muscle-residing pericytes.
abstract: Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. This study characterized the early molecular alterations in humans to eccentric contractions (ECs), a stimulus known to induce a muscle regenerative response. Thirty-five subjects completed 100 ECs of the knee extensors with 1 leg, and muscle biopsies were taken from both legs 3 h post-EC. The sample from the non-EC leg served as the control. We first conducted a well-powered transcriptomic screen and network analysis. Our screen identified significant changes in several transcripts with functions relating to inflammation, cell growth, and proliferation. Network analysis then identified the transcription factor NF-κB as a key molecular element affected by ECs. A transcription factor ELISA, using nuclear extracts from EC and control muscle samples, showed a 1.6-fold increase in NF-κB DNA binding activity following ECs. Immunohistochemical experiments localized the majority of NF-κB-positive nuclei to cells in the interstitium, which stained positive for the pericyte markers NG2 proteoglycan and alkaline phosphatase. Our results provide the first evidence of NF-κB activation in human muscle following ECs and suggest a novel role for muscle residing pericytes in the early adaptive response to ECs.
authors: Department of Kinesiology, University of Massachusetts, Amherst, MA 01003, USA. rhyldahl@kin.umass.edu
authors: Robert D
authors: RD
authors: Hyldahl
authors: Ling
authors: L
authors: Xin
authors: Monica J
authors: MJ
authors: Hubal
authors: Stephanie
authors: S
authors: Moeckel-Cole
authors: Stuart
authors: S
authors: Chipkin
authors: Priscilla M
authors: PM
authors: Clarkson