title: Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.
abstract: BACKGROUND
  Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD).
  
  
  METHODS
  In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro.
  
  
  RESULTS
  Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro.
  
  
  CONCLUSIONS
  MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. cclchen1@vghks.gov.tw.
authors.forename: C L
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. kjchou@vghks.gov.tw.
authors.forename: K J
authors.initials: KJ
authors.lastname: Chou
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. hcfang@vghks.gov.tw.
authors.forename: H C
authors.initials: HC
authors.lastname: Fang
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. cyhsu@vghks.gov.tw.
authors.forename: C Y
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. wchuang1@vghks.gov.tw.
authors.forename: W C
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. cwhuang0824@vghks.gov.tw.
authors.forename: C W
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. ckhuang@vghks.gov.tw.
authors.forename: C K
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. xychen16@gmail.com.
authors.forename: H Y
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang-Ming University, 386 Ta-Chung 1st Rd, Kaohsiung, 813, Taiwan. ptlee@vghks.gov.tw.
authors.forename: P T
authors.initials: PT
authors.lastname: Lee
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005355:Fibrosis / Q000517:prevention & control; D007668:Kidney / Q000166:cytology* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells
chemical_list: D017077:Culture Media, Conditioned