Noninvasive monitoring of pulmonary fibrosis by targeting matrix metalloproteinases (MMPs)

Yan Cai, Lei Zhu, Fan Zhang, Gang Niu, Seulki Lee, Shioko Kimura, Xiaoyuan Chen

Research output: Contribution to journalArticlepeer-review

Abstract

While idiopathic pulmonary fibrosis (PF) is a devastating lung disease, the management of PF including effective monitoring of disease progression remains a challenge. Herein, we introduce a novel, fast, and ultrasensitive metalloproteinase (MMP) activatable optical probe, named MMP-P12, to noninvasively monitor PF progression and response to PF treatment. A bleomycin (BLM)-induced mouse PF model was subjected noninvasively to optical imaging at various time points after BLM treatment. The mouse PF model developed fibrosis during 21 days of experimental period, and the progression of PF was well correlated with the stepwise increase of MMP-2 expression as examined by quantitative RT-PCR and Western blot analysis on the 7-, 14-, and 21-day post-BLM administration. On these days, MMP-activated fluorescence images were acquired in vivo and ex vivo. Signal quantification showed time-dependent lung-specific incremental increases in fluorescence signals. As a treatment for PF, secretoglobin 3A2 was daily administered intravenously for five days starting on day seven of BLM administration, which resulted in reduced MMP-2 activity and reduction of PF as previously demonstrated. Importantly, the fluorescence signal that reflected MMP activity also decreased in intensity. In conclusion, MMPs may play an important role in PF development and the MMP-P12 probe could be a promising tool for PF detection, even at an early stage of the disease as well as an indicator of therapy response.

Original languageEnglish (US)
Pages (from-to)2237-2247
Number of pages11
JournalMolecular Pharmaceutics
Volume10
Issue number6
DOIs
StatePublished - Jun 3 2013
Externally publishedYes

Keywords

  • activatable probe
  • matrix metalloproteinase
  • optical imaging
  • pulmonary fibrosis
  • secretoglobin 3A2

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Noninvasive monitoring of pulmonary fibrosis by targeting matrix metalloproteinases (MMPs)'. Together they form a unique fingerprint.

Cite this