Friday, September 25, 2026

Calcium dysregulation amplifies fibrotic responses to TGFβ in human Friedreich's ataxia fibroblasts

Calcium dysregulation amplifies fibrotic responses to TGFβ in human Friedreich's ataxia fibroblasts Anna Stepanova, Hibiki Kawamata, Giovanni Manfredi bioRxiv 2026.09.21.753166; doi: doi:10.64898/2026.09.21.753166 

Our study suggests that cytosolic Ca regulation modifies profibrotic stimulation in FA. We propose the following mechanism for intrinsic profibrotic bias in human FA fibroblasts: NCX1 downregulation contributes to slower cytosolic Ca clearance, thereby sustaining Ca-dependent signaling and consequently increased expression of CCN2 and other profibrotic factors. If validated in FA heart, our findings would identify NCX1-mediated Ca extrusion in fibroblasts as a potential therapeutic target to mitigate fibrosis that contributes to lethal cardiomyopathy in FA patients.