Stem cell factor (SCF) isoform 248 (SCF248)

Stem cell factor (SCF) isoform 248, also known as KIT ligand (KITLG) isoform 1, is a cytokine and growth factor that plays a critical role in the regulation of inflammatory and fibrotic processes (UniProt P21583, NIH). It is a 248-amino acid protein produced by alternative splicing of the KITLG gene, specifically characterized by the inclusion of exon 6, which contains a proteolytic cleavage site (PubMed 11454473, NIH). This allows the membrane-bound form to be converted into a soluble protein, both of which can bind and activate the c-KIT (CD117) receptor (PubMed 32004468). While the shorter SCF220 isoform is essential for homeostatic functions like erythropoiesis and hematopoiesis, SCF248 is predominantly upregulated in diseased tissues, driving the activation of mast cells, eosinophils, and group 2 innate lymphoid cells (ILC2) (Opsidio, PubMed 33681111). Consequently, SCF248 is a key driver in the pathogenesis of idiopathic pulmonary fibrosis (IPF), severe asthma, and other chronic inflammatory conditions (PubMed 32004468, Frontiers in Immunology). Therapeutic targeting of this specific isoform, such as with the monoclonal antibody OpSCF, is designed to inhibit pathological remodeling and inflammation while avoiding the systemic toxicities, such as anemia, associated with broad c-KIT or total SCF inhibition (Opsidio). This selective approach aims to break the feed-forward cycle of chronic inflammation and allow for natural tissue repair processes.

Other names

KIT ligand (KITLG) isoform 1KIT ligand (KITLG) isoform bSoluble stem cell factor precursorMast cell growth factor (MGF)Steel factor (SF)KL-1C-kit ligand

Selective neutralization of the SCF248 isoform to prevent activation of the c-KIT receptor on inflammatory and fibrotic cells