Similarly, Shh signaling in pancreatic fibroblasts is required for tissue repair during the onset of pancreatic cancer and pancreatitis due to a mutation in the proto-oncogene, K-ras, as a deletion of one allele of Gli1 or mice lacking expression of Shh in the pancreatic epithelium significantly impaired tissue remodeling and cytokine expression in this model [75]. Here, SHH is linked to pancreatitis.