The signalling of AT2 and the influence on the collagen metabolism of AT2 receptor in adult rat cardiac fibroblasts.

摘要

OBJECTIVES: Angiotensin (Ang) II exerts its roles on cardiac fibroblasts by two receptors: type I (AT1) and type 2 (AT2).The role of AT1 has been well known, but less is known about AT2. The present study was designed to explore signal pathways of AT2 and observe whether AT2 is involved in the collagen metabolism of cardiac fibroblasts. METHODS AND RESULTS: Adult rat cardiac fibroblasts were extracted, cultured and treated with Ang-II alone, Ang-II plus losartan or PD123319. G protein-coupled receptors signalling pathway finder gene arrays were used to analyse expression changes of 96 genes associated with 11 signal pathways. With a 10-fold change in threshold, 7 genes were differentially expressed specific to AT1 blockade associated to 5 signal pathways including PKC, PLC, MAPK, NO/cGMP and NFkappaB; while 24 genes were specific to AT2 blockade related to 10 signal pathways including cAMP/PKA, Ca2+, PKC, PTK, MAPK, PI-3K, NO/cGMP, Rho, NFkappaB and JAK-STAT. RT-PCR were used to confirm the results of arrays and measure collagen (Col) I and tissue inhibitor of metalloproteinase (TIMP)-1 mRNA levels. AT2 blockade decreased Col I and TIMP-1 mRNA levels compared to the Ang II-treated group, which was similar with AT1 blockade. CONCLUSION: In adult rat cardiac fibroblasts, AT2 was obviously distinct from AT1 in signalling responses. AT2 appeared to spread more widely than AT1. AT2 might be involved in the collagen metabolism of rat cardiac fibroblasts by regulating Col I and TIMP1 mRNA levels.