Hepatic and interstitial fibrosis in kidney is significantly increased in BCAA group. Conclusion: Branched-chain amino acid supplementation accelerates cyst growth in Pkd1flox/flox: Mx1-Cre mice. NAKAMURA JIN1, OGUCHI AKIKO1, YAMADA RYO1, TSUCHIDA JUN-ICHI2, KOHNO KENJI3, YANAGITA MOTOKO1 1Department of Nephrology, Kyoto University Graduate School of Medicine; 2Medical learn more Innovation Center, Kyoto University Graduate School of Medicine; 3Nara Institute of Science and Technology Introduction: We previously reported that most fibroblasts in the kidney cortex and outer medulla are myelin protein zero-Cre (P0-Cre) lineage-labeled cells of extra-renal origin, and
that some of them are erythropoietin (EPO) producing cells in the healthy kidney. In the diseased kidney, P0-Cre lineage-labeled cells transdifferentiate into myofibroblasts and predominantly contribute to fibrosis, with concomitant loss of EPO production. In this study, we further investigated the pathophysiological function of P0-Cre linage-labeled fibroblasts and the crosstalk between the fibroblasts and tubular epithelial cells. Methods: We utilized P0-Cre inducible simian diphtheria toxin receptor (DTR) transgenic https://www.selleckchem.com/products/dinaciclib-sch727965.html mice (P0-Cre:iDTR mice) in which Cre-mediated excision of a STOP cassette renders P0-Cre linage-labeled fibroblasts sensitive to diphtheria toxin (DT). The binding of DT to DTR halts protein synthesis
within the cells, inhibiting the crosstalk between fibroblasts and tubular epithelial cells. Results: First we confirmed that renal fibroblasts were successfully labeled with DTR in P0-Cre:iDTR mice. DT administration ablated the expression of DTR and fibroblast markers in the kidney, indicating the effective cessation of protein synthesis in P0-Cre linage-labeled fibroblasts. Simultaneously, the expression of EPO was significantly reduced, and did not increase even after the induction of severe anemia. In addition, the expression of tubular injury markers, as well as the proliferation of proximal tubule cells was induced. The administration of DT to P0-Cre:iDTR mice with unilateral ureteral Microbiology inhibitor obstruction reduced the expression of
fibrosis markers, and enhanced the expression of tubular injury markers in diseased kidney. Unlike the results of healthy kidney, tubular proliferation in diseased kidney was attenuated. Conclusion: Cessation of protein synthesis in P0-Cre linage-labeled fibroblasts reduced the expression of EPO in healthy kidney and the fibrosis markers in diseased kidney, supporting our previous findings. And this also induced the tubular injury and influenced the tubular proliferation, suggesting that fibroblasts inhibit tubular proliferation and injury in healthy kidney, while support the repair of injured tubule by promoting tubular proliferation in diseased kidney. These results indicate the possible interactions between the fibroblasts and tubular epithelial cells. We are currently searching for the molecules responsible for the interactions.