Differential changes of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in human serum and biopsy samples in ulcerative colitis and Crohn's disease

Sándor, Zsolt; Szabó, S; Szathmári, Miklós; Zágoni, Tamás; Tulassay, Z

doi:10.1016/s0016-5085(98)84373-4

Cited by 2 publications

(1 citation statement)

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“…In liver fibrosis, increased levels of PDGF-BB are derived from infiltrating macrophages (1,14), which may also occur in the inflamed intestine. For example, elevated levels of PDGF-BB have been described in both serum and biopsy samples in IBD (16,33), where both PDGF-BB and PDGF-R␤ may be present in inflamed intestinal regions (20). However, the permissive events that regulate the early onset of growth factor receptor expression and CSMC hyperplasia as well as their subsequent downregulation remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Mitogenic factors promoting intestinal smooth muscle cell proliferation

Stanzel

Lourenssen

Nair

et al. 2010

American Journal of Physiology-Cell Physiology

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Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colon. While platelet-derived growth factor (PDGF)-AA, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were ineffective, PDGF-BB and insulin-like growth factor-1 (IGF-1) caused significant increase in [(3)H]thymidine incorporation, bromodeoxyuridine uptake, and increased CSMC number, with PDGF-BB (≥0.2 nM) substantially more effective than IGF-1. Surprisingly, CSMC lacked expression of PDGF receptor-β (PDGF-Rβ) upon isolation but by 4 days in vitro, CSMC gained expression of PDGF-Rβ as shown by quantitative PCR, Western blot analysis, and immunocytochemistry; these CSMC responded to PDGF-BB but not IGF-1. PDGF-BB caused PDGF-Rβ phosphorylation and mobilization from the surface membrane, leading to activation of both Akt and ERK signaling pathways, which were essential for subsequent proliferation. In contrast, PDGF-AA, FGF, EGF, and IGF-1 were ineffective. In vivo, control CSMC lacked expression of PDGF-Rβ. However, this changed rapidly with TNBS-colitis, and by day 2 when CSMC proliferation in vivo is maximal, freshly isolated CSMC showed on-going PDGF-Rβ phosphorylation that was further increased by exogenous PDGF-BB. This suggests that the onset of PDGF-Rβ expression is a key factor in CSMC growth in vitro and in vivo, where inflammation may damage intrinsic inhibitory mechanisms and thus lead to hyperplasia.

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