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BM-derived cells can contribute to repair of the renal peritubular capillary (PTC) network following acute ischemic injury. However, the cell fate and regulation of BM-derived cells during the progression of chronic renal disease remains unclear. Using chimeric mice transplanted with enhanced green fluorescent protein (EGFP)-expressing BM, we demonstrate that the number of BM-derived myofibroblasts coincided with the development of fibrosis in a mouse adriamycin (ADR)-induced nephrosis model of chronic, progressive renal fibrosis. Four weeks after ADR injection, increased numbers of BM-derived myofibroblasts were observed in the interstitium of ADR-injected mice. Six weeks after ADR injection, more than 30% of renal \u03b1-smooth muscle actin (+) (\u03b1-SMA+) interstitial myofibroblasts were derived from the BM. In addition, BM-derived cells were observed to express the endothelial cell marker CD31 and the myofibroblast marker \u03b1-SMA. Blockade of p38 mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-\u03b21\/Smad2 signaling was found to protect BM-derived PTC endothelial cells and inhibit the number of BM-derived von Willebrand factor (vWF)(+)\/EGFP(+)\/\u03b1-SMA(+) cells, EGFP(+)\/\u03b1-SMA(+) cells, and total \u03b1-SMA(+) cells in ADR-injected mice. Inhibition of the p38 MAPK and TGF-\u03b21\/Smad signaling pathways enhanced PTC repair by decreasing endothelial-myofibroblast transformation, leading to structural and functional renal recovery and the attenuation of renal interstitial fibrosis. Investigation of the signaling pathways that regulate the differentiation and survival of BM-derived cells in a progressive disease setting is vital for the successful development of cell-based therapies for renal repair.<\/jats:p>","DOI":"10.1634\/stemcells.2006-0133","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T01:39:54Z","timestamp":1166146794000},"page":"697-706","source":"Crossref","is-referenced-by-count":97,"title":["The Contribution of Bone Marrow-Derived Cells to the Development of Renal Interstitial Fibrosis"],"prefix":"10.1093","volume":"25","author":[{"given":"Jinhua","family":"Li","sequence":"first","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Monash University, Victoria, 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