A new experimental study published in The Journal of Pathology examines the role of fibroblast-derived neuropilin 1 in the progression of renal fibrosis, providing mechanistic insight into how fibroblast behavior influences chronic kidney disease.
Renal fibrosis represents a final common pathway in chronic kidney disease, characterized histologically by excessive extracellular matrix deposition and accumulation of myofibroblasts. Resident kidney fibroblasts are now recognized as the principal source of these myofibroblasts, making their activation state a key focus in experimental pathology and disease modeling. However, the molecular regulators that determine whether fibroblast activation resolves or progresses to chronic fibrosis remain incompletely defined.
Using mouse models, researchers selectively deleted fibroblast-derived neuropilin 1 (NRP1) in kidney-resident fibroblasts and evaluated outcomes in two established models of kidney injury: unilateral ureteral obstruction and folic acid–induced nephrotoxicity. In both models, kidneys lacking fibroblast NRP1 developed more severe interstitial fibrosis. Histologic analyses showed increased collagen deposition, expansion of alpha–smooth muscle actin–positive myofibroblasts, and poorer preservation of kidney architecture compared with controls.
The findings indicate that fibroblast activation is not uniform. Fibroblasts lacking NRP1 demonstrated reduced proliferation during early injury and were more likely to transdifferentiate into myofibroblasts during chronic injury. Together, these results suggest that NRP1 supports a reparative fibroblast state and limits progression to maladaptive fibrosis.
Researchers also analyzed publicly available single-cell RNA sequencing data from human kidney samples. NRP1 expression was enriched in fibroblast populations associated with inflammation and wound healing rather than in fully differentiated, matrix-producing myofibroblasts. This observation reinforces the concept of fibroblast heterogeneity and may help explain variability in fibrosis severity and pattern among patients with similar clinical diagnoses.
The findings highlight several points relevant to renal pathology research. Fibroblast phenotype and signaling context may influence fibrosis severity independently of the initiating injury. In addition, markers such as NRP1 may help refine interpretation of fibroblast populations in immunostained tissue sections and single-cell datasets.
While the study is preclinical and does not propose immediate diagnostic applications, it provides mechanistic context that may inform future biomarker development and improve understanding of fibrotic patterns encountered in chronic kidney disease research and pathology practice.
The authors declared having no competing interests.
Source: The Journal of Pathology
