Children's National Health System Posters

Title

IPSE, a urogenital parasite derived protein, drives urothelial proliferation and alleviates chemotherapy induced hemorrhagic cystitis

Poster Number

348

Document Type

Poster

Status

Postdoc

Abstract Category

Basic Biomedical Sciences

Keywords

anti-inflammatory, hemorrhagic cystitis, ifosfamide, IPSE, urothelium

Publication Date

Spring 2018

Abstract

Introduction and Objective: Chemotherapy-induced hemorrhagic cystitis can be a difficult-to-manage complication. We previously reported that a single dose of H-IPSEH06, a Schistosoma haematobium-derived host immunomodulatory protein, is superior to three doses of Mesna in preventing ifosfamide-induced hemorrhagic cystitis. Herein, we expand upon this work in three directions: 1) characterization of H-IPSEH06’s influence over urothelial proliferation; 2) elucidating the mechanism of IPSE’s therapeutic effect through transcriptional profiling.

Methods: Recombinant H-IPSE or an NLS mutant of IPSE (H-IPSENLS) was incubated with mouse and human urothelial cell lines, and proliferation and cell cycle status measured by flow cytometry using CFSE and propidium iodide, respectively. Cellular RNA were isolated and subjected to RNA-seq analysis. Mice were administered H-IPSEH06 or H-IPSENLS, challenged with ifosfamide, and their bladder RNA subjected to RNA-seq analysis.

Results: H-IPSEH06 increased both mouse and human urothelial cell proliferation, and drove cells towards S-phase. These effects are NLS dependent, and are consistent with H-IPSEH06’s ability to protect the urothelium following ifosfamide challenge. RNA-seq analysis revealed that several cell proliferation related pathways were differentially expressed between H-IPSEH06 vs vehicle-treated mice challenged with ifosfamide. Also, multiple muscle contraction-related pathways are differentially expressed between H-IPSEH06 vs H-IPSENLS-treated mice challenged with ifosfamide. These findings are consistent with H-IPSEH06’s ability to prevent ifosfamide induced bladder dysfunction.

Conclusion: H-IPSEH06 continues to prove to be a promising prophylactic against chemotherapy-induced hemorrhagic cystitis. Our mechanistic studies on H-IPSEH06 suggest potential means by which to optimize this molecule’s NLS-dependent therapeutic effects.

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IPSE, a urogenital parasite derived protein, drives urothelial proliferation and alleviates chemotherapy induced hemorrhagic cystitis

Introduction and Objective: Chemotherapy-induced hemorrhagic cystitis can be a difficult-to-manage complication. We previously reported that a single dose of H-IPSEH06, a Schistosoma haematobium-derived host immunomodulatory protein, is superior to three doses of Mesna in preventing ifosfamide-induced hemorrhagic cystitis. Herein, we expand upon this work in three directions: 1) characterization of H-IPSEH06’s influence over urothelial proliferation; 2) elucidating the mechanism of IPSE’s therapeutic effect through transcriptional profiling.

Methods: Recombinant H-IPSE or an NLS mutant of IPSE (H-IPSENLS) was incubated with mouse and human urothelial cell lines, and proliferation and cell cycle status measured by flow cytometry using CFSE and propidium iodide, respectively. Cellular RNA were isolated and subjected to RNA-seq analysis. Mice were administered H-IPSEH06 or H-IPSENLS, challenged with ifosfamide, and their bladder RNA subjected to RNA-seq analysis.

Results: H-IPSEH06 increased both mouse and human urothelial cell proliferation, and drove cells towards S-phase. These effects are NLS dependent, and are consistent with H-IPSEH06’s ability to protect the urothelium following ifosfamide challenge. RNA-seq analysis revealed that several cell proliferation related pathways were differentially expressed between H-IPSEH06 vs vehicle-treated mice challenged with ifosfamide. Also, multiple muscle contraction-related pathways are differentially expressed between H-IPSEH06 vs H-IPSENLS-treated mice challenged with ifosfamide. These findings are consistent with H-IPSEH06’s ability to prevent ifosfamide induced bladder dysfunction.

Conclusion: H-IPSEH06 continues to prove to be a promising prophylactic against chemotherapy-induced hemorrhagic cystitis. Our mechanistic studies on H-IPSEH06 suggest potential means by which to optimize this molecule’s NLS-dependent therapeutic effects.