Stimulus-driven down-regulation of IR in NL fibroblasts may ultimately serve as a mechanism of reducing the available pool of receptors capable of being activated, thus acting as a dampening mechanism for receptor activation and subsequent signal transduction in NL, the likes of which is transient (in IPF at 6 hr) or absent (in SSc) in fibrosing lung conditions. This evidence concerns the gene INSR and systemic sclerosis.