Based on these experiments, the primary species responsible for transducing the fibrotic signal leading to ECM secretion in SSc appears to be a combination of the IGF1R and IR receptors, possibly existing as an IGF1R/IR hybrid heteroreceptor form; whereas, there appears to be a greater contribution of IGF1R homodimers in addition to the possible IGF1R/IR hybrid receptors that transduce the IGF-II signal in NL, suggesting an IGF-II-driven receptor species shift in pathologic lung conditions associated with increased levels of IGF-II. Here, INSR is linked to systemic sclerosis.