Work

Promoting activities of human cyclophilin A on calcium oxalate stone formation at crystal growth, aggregation and crystal-cell adhesion phases

Year: 2025

Type: article

Abstract: Kidney stone is a specialized form of biomineralization involving complex interactions between crystals and urinary macromolecules. Renal tubular cells secrete cyclophilin A (CyPA), a protein whose elevated level is associated with various kidney diseases. Nevertheless, its role in kidney stone formation has not previously been explored. This study thus aimed to investigate roles of CyPA in kidney stone formation through various calcium oxalate (CaOx) crystal assays. Recombinant human CyPA was generated to mimic its secretory form excreted into the urine. Crystal assays yielded the first evidence demonstrating that CyPA significantly promoted CaOx growth, aggregation and crystal-cell adhesion, all of which are the critical steps during initial CaOx stone formation. Despite the lack of specific Ca 2+ -binding and Ox 2− -binding domains and its inability to bind free Ca 2+ /Ox 2− ions in solution, CyPA demonstrated a distinct ability to bind CaOx crystals. Upon binding, CyPA facilitated further CaOx growth, aggregation of adjacent crystals and crystal-cell adhesion. These findings unravel a novel mechanism of kidney stone pathogenesis, expanding the known functions of CyPA. This research also provides solid evidence of how CyPA became one of the compositions in the stone matrix and highlights its potential to be a therapeutic/preventive target for management/prevention of kidney stone disease. • Recombinant human CyPA was successfully constructed, expressed and purified. • CyPA did not affect CaOx crystallization and did not bind Ca 2+ - and Ox 2− ions. • CyPA promoted CaOx growth, aggregation and crystal-cell adhesion. • CyPA-CaOx crystal binding was responsible for its CaOx-promoting activities.

Source: International Journal of Biological Macromolecules

DOI: 10.1016/j.ijbiomac.2025.143374

Authors: Sudarat Hadpech, Waralee Srinarawat, Visith Thongboonkerd

Institutions: Siriraj Hospital, Mahidol University

Language: English

Topic: Kidney Stones and Urolithiasis Treatments

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390