Discovery May Advance Targeted Therapies for Chronic Fibrotic Disease

Researchers at Cincinnati Children’s have identified Gucy1α1 as a novel specific marker of fibrosis in kidney, heart, lung and liver fibroblasts–a discovery that may have significant implications for treating multiple chronic diseases characterized by fibrosis.

Several human organs can be damaged by progressive fibrosis, including chronic kidney disease (CKD). In fact, about 14% of U.S. adults have CKD, including more than one third of those aged 65 and up, according to the United States Renal Data System. However, the complexity of the molecular and cellular mechanisms involved in fibrosis have slowed efforts to develop targeted treatments. Current approaches to trace and target activated fibroblasts lack the specificity needed to be safe and effective.

Study Reveals Promising Strategy to Examine Fibroblasts

A study published Nov. 26, 2024, in Scientific Reports, led by first author Valeria Rudman-Melnick, MD, PhD, and corresponding author Prasad Devarajan, MD, of the Division of Nephrology and Hypertension, examined how expression of the Gucy1α1 gene and protein changes over time in pre-clinical models of chronic kidney disease. The findings reveal that Gucy1α1 strongly labels kidney fibroblasts, including fractions expressing currently used fibrosis markers such as αSma, Pdgfrβ and Vim, throughout the injury progression.

“This discovery is important because, unlike classically used non-specific markers, Gucy1α1 specifically and comprehensively labels only fibroblasts, without overlapping with several other off-target populations,” Devarajan says.

In addition to the pre-clinical model findings, the research team found robust and specific Gucy1α1 expression in fibroblasts in chronically injured human kidney and lung tissues. Gucy1α1 also has been shown as a fibroblast marker in pre-clinical models of cardiac and liver fibrosis.

“Given its specific expression profile, targeting Gucy1α1 offers a promising strategy to mechanistically examine fibroblasts in future studies with immense translational potential in multiple organs plagued by disease progression,” Devarajan says.

(Published April 2025)

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