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The real origin of fibroblast during the development of renal fibrosis is still uncertain. In a recent paper by Asada and colleagues the Authors demonstrated that the majority of Erythropoietin-producing fibroblasts in the healthy kidney originate from myelin-positive extra renal cells. During the development of renal fibrosis, these extrarenal fibroblast trans-differentiated into myofibroblasts with concomitant loss of erythropoietin production. These intriguing data might lead to the development of new drugs both capable to reduce renal fibrosis and preserve the production of endogenous Erythropoietin.