Background. In many resource-limited countries, children are routinely given intramuscular (IM) injections of medication to treat pain or illness. IM injections are suspected in the development of gluteal fibrosis (GF) in children, a condition that limits normal hip motion and function. The mechanism by which GF develops is not understood. Our study examines a commonly IM administered antimalarial in Uganda, quinine, to assess its ability to cause fibrogenesis of muscle fibro/adipogenic progenitors (FAPs), the cellular source of muscle fibrosis. The purpose was to evaluate if quinine itself could alter muscle cells and cause fibrosis. Methods. FAPs were isolated from skeletal muscle in wildtype C57BL/6 mouse with florescence-activated cell sorting (FACS). After sorting, the FAPs were cultured in standard media until they reached 80% confluence. The cells were then cultured in a series of quinine concentrations. Fibrogenesis of FAPs was determined with RT-qPCR of fibrogenic markers.Results. The RT-PCR results showed increased αSMA, vimentin and collagen-1 expression in quinine exposed cells. At lower quinine dosages, expression increased in stemness markers; Sox2, cMyc, Oct-4, and Nanog. Conversely, at higher dosages quinine decreased stemness marker expression. Lastly, quinine increased TGFβ1 and Ki67 and decreased BMP7. Conclusions. Our findings suggest that quinine induces FAP fibrogenesis and reduces FAP stemness. Further study is needed, but if confirmed that Quinine induces fibrogenesis, limiting the use of Quinine may be an effective public health intervention to reduce cases of gluteal fibrosis and resultant childhood disability.
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