Heart Transplantation in Systemic Sclerosis: New Impulses for Conventional Scleroderma Transplantation Regimen and Scleroderma Diagnostic Monitoring: 2 Case Reports

Faust, Isabel; Weile, Jan; Fujita, Buntaro; Kandolf, Reinhard; Hendig, Doris; Vollmer, Tanja; Stan, Alina; Kellner, Udo; Kühn, Joachim; Gummert, J; Knabbe, Cornelius

doi:10.1016/j.transproceed.2019.01.025

Cited by 9 publications

(1 citation statement)

References 21 publications

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“…Considering the complex mechanisms that are involved in fibroproliferative diseases, macrophages are a crucial cell type which modulate the fibrotic process and its resolution [ 11 ]. Increased serum XT activity and/or cellular XYLT1 expression have been identified as biochemical markers for assessing fibrotic remodeling processes, such as the cytokine-mediated fibroblasts-to-myofibroblasts transition in SSc [ 21 , 27 , 28 , 45 ]. Given the missing link between fibrotic XT activity increase and XT regulation in immune cells, this study aimed to investigate the impacts of macrophage polarization on XT-I expression and activity.…”

Section: Discussionmentioning

confidence: 99%

The Human Myofibroblast Marker Xylosyltransferase-I: A New Indicator for Macrophage Polarization

Wolny

Lindenkamp

et al. 2022

Biomedicines

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Chronic inflammation and excessive synthesis of extracellular matrix components, such as proteoglycans (PG), by fibroblast- or macrophage-derived myofibroblasts are the hallmarks of fibrotic diseases, including systemic sclerosis (SSc). Human xylosyltransferase-I (XT-I), which is encoded by the gene XYLT1, is the key enzyme that is involved in PG biosynthesis. Increased cellular XYLT1 expression and serum XT-I activity were measured in SSc. Nothing is known so far about the regulation of XT-I in immune cells, and their contribution to the increase in measurable serum XT-I activity. We utilized an in vitro model, with primary human CD14+CD16+ monocyte-derived macrophages (MΦ), in order to investigate the role of macrophage polarization on XT-I regulation. The MΦ generated were polarized towards two macrophage phenotypes that were associated with SSc, which were classified as classical pro-inflammatory (M1-like), and alternative pro-fibrotic (M2-like) MΦ. The fully characterized M1- and M2-like MΦ cultures showed differential XT-I gene and protein expressions. The fibrotic M2-like MΦ cultures exhibited higher XT-I secretion, as well as increased expression of myofibroblast marker α-smooth muscle actin, indicating the onset of macrophage-to-myofibroblast transition (MMT). Thus, we identified XT-I as a novel macrophage polarization marker for in vitro generated M1- and M2-like MΦ subtypes, and broadened the view of XT-I as a myofibroblast marker in the process of MMT.

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