This 93-residue, cysteine-rich granulin precursor (MW = 88 kDa; Symbol: PGRN), also called proepithelin and PC cell-derived growth factor, is a pleiotrophic growth factor with important roles in maintaining and regulating the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host-defense. PGRN also has potent antiinflammatory properties, and its deregulation is associated with rheumatoid arthritis and inflammatory bowel disease. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Recombinant PGRN protein strongly inhibits TNF and the expression of interferon-γ-induced chemokines CXCL9 and CXCL10. Moreover, in PGRNnull mice, many chemokines, including CXCL9 and CXCL10, are significantly induced.
