REGULATION OF HYPERTENSION-INDUCED RENAL INJURY BY INDUCTION OF SMOOTH MUSCLE ACTIN BINDING PROTEIN EXPRESSION

在自发性高血压大鼠(SHR)中，已经建立了碱性钙蛋白(BCN-TG)高表达的转导基因，它是一种平滑肌肌动蛋白结合蛋白。与野生型SHR相比，BCN-TG的高血压发病时间延迟。培养BCN-TG系膜细胞和野生型SHR系膜细胞。与野生型SHR相比，BCN-TG对PDGF-BB诱导的系膜细胞增殖活性有明显抑制作用。因此，诱导BCN可抑制高血压的发生和肾小球系膜细胞的增殖，这可能有利于高血压的治疗和高血压相关性肾损伤的治疗。为探讨BCN在高血压肾损害中的作用，用BCN和野生型SHR诱导大鼠抗Thy-1肾炎模型。与野生黑麦自发性高血压大鼠相比，抗Thy-1肾炎大鼠肾小球系膜细胞增殖和活化均受到明显抑制(以α-平滑肌肌动蛋白表达为指标)。随后的IV型胶原在肾小球中的积聚在BCN中也受到显著抑制。综上所述，BCN诱导将是治疗高血压及高血压相关肾损伤的有效策略。

Trasnsgenic for overexpression of basic calponin (bCN-Tg), smooth muscle actin binding protein, has been established in spontaneous hypertension rat (SHR). Onset of hypertension delayed in bCN-Tg compared to wild type SHR. Mesangial cells from both bCN-Tg and wild type SHR were cultured. Proliferative activity induced by PDGF-BB was significantly suppressed in mesangial cells from bCN-Tg than those from wild type SHR. From these, bCN induction resulted in suppression of the onset of hypertension and mesangial cell proliferation, that may be beneficial for the treatment of both hypertension and hypertension-related renal injuries. To study the role of bCN in renal injury associated with hypertension, anti Thy-1 nephritis was induced in both bCN and wild type SHR. Both glomerular cell proliferation and activation of mesangial cells evaluated by the expression of α-smooth muscle actin were significantly suppressed in anti Thy-1 nephritis in bCN compared to wild rye SHR. Subsequent type IV collagen accumulation in glomeruli was also significantly suppressed in bCN. In conclusion, bCN induction will be a powerful strategy for hypertension and hypertension associated renal injuries.