SCF is a paracrine cytokine produced by fibroblasts, keratinocytes, and endothelial cells . SCF and its receptor c-kit play an essential role in hemopoiesis and maintaining hematopoietic stem cell survival, mast cell stimulation, mediating the function of the pancreas, and melanogenesis . A mutation in SCF could cause anemia, lack of mast cells, immaturity and loss of functions of pancreatic endocrine cells, and disappearance of pigmentation, as well as the absence of melanocytes . c-Kit is a receptor tyrosine kinase expressed on melanocytes. It has two domains containing a glycosylated extracellular ligand-binding domain, comprising five Ig-like domains, and a cytoplasmic region, which comprises the protein tyrosine kinase domain. At the ectodomain, five Ig-like domains are separated from the first three domains, constituting a ligand-binding area, and two other domains act on monomerization or dimerization of c-kit. Another part, the phosphorylation site, is situated in the intracellular region, consisting of the juxtamembrane area and a large kinase-insert region . Binding of SCF to c-kit stimulates dimerization and initiation of catalytic activities of autophosphorylation and tyrosine kinase to complete its signal transmission. Y721 phosphorylation of c-kit is involved in the phosphoinositide 3-kinase (PI3K) pathway. PI3K does not only regulate cell survival but also cause pigmentation by increasing the serine/threonine-specific protein kinase AKT activity, which can produce phosphorylate glycogen synthase kinase 3β (GSK-3β) and lead to β-catenin accumulation, resulting in translocation to the nucleus to increase MITF activity . c-Kit phosphorylation at Y703 and Y936 activates the mitogen-activated protein kinase (MAPK) pathway and leads to cell proliferation, differentiation, and melanin alteration . The activated extracellular signal-related kinase ERK and c-Jun N-terminal kinase JNK, the members of the MAPK family, upregulate the transcription activity or ubiquitin-dependent degradation of MITF as a feedback mechanism of melanin production. On the other hand, the activated p38 induces phosphorylation of CREB and then activates MITF to promote tyrosinase transcription . The other phosphorylation sites such as Y586, Y570, Y900, Y568, Y570, and Y730 are involved in cell proliferation, survival, adhesion, and differentiation, and Y586, Y570, and Y936 participate in receptor downregulation. Some studies even indicated clearly increased expression of SCF was observed after UV light exposure, especially UVB, in both keratinocytes and fibroblasts, which facilitated melanogenesis behavior . In addition, SCF is released in greater levels by fibroblasts than by keratinocytes . Several studies have demonstrated the functions of SCF, irrespective of its secretion by keratinocytes or fibroblasts, in proliferation, differentiation, and melanogenesis of melanocytes; however, the importance of SCF and its effect on other paracrine factors are yet to be determined . Furthermore, fibroblasts play an important role in regulating skin color, and the expression level of SCF in fibroblasts is more than that in keratinocytes. Therefore, it is of particular interest to understand the influence on SCF in terms of whether its dysfunction is occurring in fibroblasts and then the alteration of other cytokines produced by fibroblasts, as well as melanogenesis in melanocytes. This study examined whether SCF silencing influences other paracrine factors secreted by fibroblasts and the changes in melanogenesis of melanocytes.