Adiponectin suppresses stiffness-dependent, profibrotic activation of lung fibroblasts

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible respiratory disease with limited therapeutic options. A hallmark of IPF is excessive fibroblast activation and extracellular matrix (ECM) deposition. The resulting increase in tissue stiffness amplifies fibroblast activation and drives disease progression. Dampening stiffness-dependent activation of fibroblasts could slow disease progression. We performed an unbiased, next-generation sequencing (NGS) screen to identify signaling pathways involved in stiffness-dependent lung fibroblast activation. Adipocytokine signaling was downregulated in primary lung fibroblasts (PFs) cultured on stiff matrices. Re-activating adipocytokine signaling with adiponectin suppressed stiffness-dependent activation of human PFs. Adiponectin signaling depended on CDH13 expression and p38 mitogen-activated protein kinase gamma (p38MAPK

• Nemeth, J.
• Skronska-Wasek, W.
• Keppler, S.
• Schundner, A.
• Groß, A.
• Schoenberger, T.
• Quast, K.
• El Kasmi, K. C.
• Ruppert, C.
• Günther, A.
• Frick, M.