Temporal and spatial mRNA expression patterns of TGF-beta1, 2, 3 and TbetaRI, II, III in skeletal muscles of mdx mice.
To address potential regulatory roles of TGF-beta1 in muscle inflammation and fibrosis associated with dystrophin deficiency, we performed quantitative RT-PCR and in situ hybridization to characterize the temporal and spatial mRNA expression patterns of TGF-beta1 and other TGF-beta subfamily members, TGF-beta2 and TGF-beta3, as well as their receptors, in quadriceps and diaphragm muscles of mdx mice. TGF-beta1 mRNA was markedly upregulated in the endomysial inflammatory cells and regenerating fibers of mdx quadriceps and diaphragm, with the mRNA levels correlated with the degree of endomysial inflammation. Upregulation of TGF-beta2, beta3, and their receptors was also appreciated but to a much lesser degree. While high levels of TGF-beta1 mRNA remained in the aging mdx quadriceps but not the diaphragm, progressive fibrosis only occurred in the diaphragm. Our data support a regulatory role for TGF-beta1 in muscle inflammation in mdx mice. It also suggests different susceptibility of quadriceps and diaphragm muscles to fibrosis induced by TGF-beta1 signaling pathway.
Zhou
Lan
L
Department of Neurology, The Cleveland Clinic Foundation, 9500 Euclid Avenue/S90, Cleveland, OH 44195, USA. zhoul2@ccf.org
Porter
John D
JD
Cheng
Georgiana
G
Gong
Bendi
B
Hatala
Denise A
DA
Merriam
Anita P
AP
Zhou
Xiaohua
X
Rafael
Jill A
JA
Kaminski
Henry J
HJ
D000818:Animals; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta