Key result
TGF-β1 exerted dualistic effects on primary human lung fibroblasts, inducing proliferation in serum-free conditions but significantly inhibiting proliferation in a mitogenic environment via p38δ MAP kinase-dependent PGE2 production.
TGF-beta exerts dualistic effects on lung fibroblasts, promoting proliferation in resting cells but inhibiting it via p38 MAP kinase and PGE2 in a mitogenic environment.
TGF-β1 dualism in lung fibroblasts should not yet guide therapy; leaves open p38δ-PGE2 targeting in fibrotic disease models.
Rationale: Inflammation, increased fibroblast proliferation, and increased deposition of extracellular matrix (ECM) are hallmarks of early lung fibrosis and asthma. Transforming growth factor-(TGF-) has been suggested as a key regulator of lung tissue homeostasis with several and often opposite effects on fibroblast proliferation and ECM production. In human and animal model systems, it has been shown that TGF-induced several signaling cascades including Smads, p38 mitogen-activated protein (MAP) kinases, and extracellular signal-regulated kinases 1/2 (ERK). Information on how TGF-regulates and controls normal primary lung fibroproliferation and ECM production is not present.
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Hostettler et al. (2009) studied Normal human lung tissue (in vitro). TGF-β1 vs. Control (serum-free medium or medium with 10% FBS) was evaluated on Fibroblast proliferation (p=<0.02). TGF-β1 exerted dualistic effects on primary human lung fibroblasts, inducing proliferation in serum-free conditions but significantly inhibiting proliferation in a mitogenic environment via p38δ MAP kinase-dependent PGE2 production.
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