These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Keratinocyte Growth Factor Reduces Injury and Leads to Early Recovery from Cyclophosphamide Bladder Injury.
    Author: Narla ST, Bushnell DS, Schaefer CM, Nouraie M, Bates CM.
    Journal: Am J Pathol; 2020 Jan; 190(1):108-124. PubMed ID: 31654636.
    Abstract:
    Keratinocyte growth factor (KGF) improves cyclophosphamide-induced bladder injury. To understand the mechanisms, we subcutaneously administered KGF to mice 24 hours before i.p. cyclophosphamide administration, followed by histologic assays and immunostaining. In vehicle (phosphate-buffered saline)-pretreated mice, nonapoptotic superficial cell death from 2 to 6 hours and apoptosis in intermediate and basal cells from 4 to 24 hours was observed after cyclophosphamide. Despite superficial cell loss, KGF suppressed intermediate and basal cell apoptosis, likely via AKT signaling. At 6 and 24 hours after cyclophosphamide, KGF-pretreated mice also had apparent extracellular signal-regulated kinase (ERK)-driven proliferation of mostly keratin 5 (KRT5)+/KRT14- intermediate cells. At 1 to 28 days after cyclophosphamide treatment, mostly KRT14+ basal progenitor cells proliferated in response to injury, peaking at 3 days in both treatment groups; however, proliferation rates were lower in the KGF group at 3 days, consistent with less injury. Three days after injury, unlike controls, KGF-pretreated mice had regenerated superficial cells. At 10 and 28 days after cyclophosphamide treatment, KGF-pretreated mice had little proliferation and marked restoration of urothelial layers, whereas the phosphate-buffered saline group had ongoing regeneration. Administration of KGF to uninjured mice reproduced ERK-driven KRT5+/KRT14- proliferation seen in injured mice; KRT14+ cells were unaffected. KGF pretreatment blocks cyclophosphamide-induced intermediate and basal cell apoptosis, likely by phosphorylated AKT, and drives phosphorylated ERK-mediated KRT5+/KRT14- cell proliferation, leading to early urothelial regeneration.
    [Abstract] [Full Text] [Related] [New Search]