Regulation of Annexin A1 expression in renal interstitial fibroblasts during chronic kidney disease

Abstract

Aim of the present study was to characterize the expression of the anti‐inflammatory and anti‐fibrotic protein annexin A1 (ANXA1) in renal fibroblasts in a rat low nephron number model of chronic kidney disease (CKD). Expression and distribution of ANXA1 was studied by real time PCR and double labeling immunofluorescence with Ecto‐5′‐nucleotidase (5′NU) as a marker for cortical fibroblasts and alpha‐smooth muscle actin (α‐sma) as marker for myofibroblasts. At ten month of age, animals with CKD were hypertensive (162 ± 5 vs. 124 ± 4 mmHg) and demonstrated a significantly increased abundance of ANXA1 immunoreactive cells in the renal cortical interstitium. ANXA1 mRNA levels were increased as well (+190 ± 34%, p<.05). 5′NU positive fibroblasts were identified as the dominant ANXA1 expressing interstitial cell type both, in controls and in animals with CKD whereas myofibroblasts in the CKD animals did not show ANXA1 signal. Treatment of cultured human fibroblasts with the pro‐fibrotic cytokine transforming growth factor beta (7,5 ng/ml for 48h) resulted in an augmented α‐sma and collagen I biosynthesis whereas ANXA1 expression was reduced. In conclusion, our results thus identify renal cortical interstitial fibroblasts as a major source for renal ANXA1 in controls and during CKD. Modulation of fibroblast ANXA1 expression may be an important mechanism for the control of extracellular matrix synthesis.