Lung Peptide PTHrP1-34 Drives Pulmonary Fibrosis and May Be a New Treatment Target | Research

The takeaway

PTHrP1-34 peptide from bronchial epithelial cells drives fibroblast activation and lung fibrosis in IPF, and targeting the PTHrP/PTH1R axis with antibodies, peptides, or gene silencing attenuated disease in mice.

3 blocking strategies worked
Antibodies, peptides, and gene silencing targeting PTHrP1-34/PTH1R all reduced pulmonary fibrosis in mice

What the researchers found

PTHrP1-34 was elevated in IPF lung tissue and bronchoalveolar lavage, activated fibroblasts and ECM production, and targeting the PTHrP1-34/PTH1R axis with antibodies, peptides, or gene silencing attenuated pulmonary fibrosis in mice.

Why it matters

IPF affects 3 million people worldwide with a median survival of 3-5 years. A new druggable peptide target could lead to the first disease-modifying therapy.

How the study worked

Bulk and single-cell RNA-seq reanalysis of human IPF tissue, immunohistochemistry in IPF patients and bleomycin-treated mice, cell-based fibroblast activation assays, and preclinical evaluation of three therapeutic strategies in bleomycin mouse model.

What this study cannot tell us

Bleomycin mouse model doesn't fully replicate human IPF. Therapeutic strategies tested short-term. Human clinical translation needs validation.

How to read the evidence

Multi-modal study with human tissue validation, cell biology, and three preclinical therapeutic approaches. Strong evidence for a novel target.

When this study was published

Published in 2025.

The bigger picture

Identifying a specific paracrine peptide driving fibrosis opens a new therapeutic avenue that could complement existing antifibrotic drugs for IPF.

Questions still open

Could PTHrP1-34 blocking be combined with existing IPF drugs (nintedanib, pirfenidone)?
Is PTHrP1-34 elevated in other fibrotic diseases beyond the lung?
What is the optimal therapeutic modality for targeting the PTHrP/PTH1R axis clinically?

Common questions

What is IPF and why is it hard to treat?

Idiopathic pulmonary fibrosis progressively scars the lungs, making breathing increasingly difficult. Current drugs slow but don't stop the disease. Finding what drives the scarring could lead to better treatments.

How does this peptide cause lung scarring?

PTHrP1-34 is released by airway lining cells and activates fibroblasts (scar-forming cells) through the PTH1R receptor. Blocking this peptide-receptor interaction reduced fibrosis in three different ways in mouse models.

Read the original research

Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.

Signal transduction and targeted therapy, 11(1)

View on PubMed ↗Publisher’s paper ↗

Citation

Fang, Xue-Quan; Lim, Suha; Lee, Yoon-Mi; Lim, Chang-Hoon; Kim, Han-Byeol; Joo, Jeong Ho; Han, Sang-Woo; Kim, Seohyun; Kim, Ji Hyung; Na, Kwon Joong; Park, Samina; Kim, Young Tae; Park, Jimyung; Park, Jooho; Lee, Jeong Seok; Shin, Eun-Young; Kim, Eung-Gook; Shin, Hyun-Woo; Lim, Ji-Hong. (2026). Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.. Signal transduction and targeted therapy, 11(1). https://doi.org/10.1038/s41392-026-02578-8