Independent Report Reveals Some Unanswered Questions On ErbB

00 �� 0.02 versus SHR, 0.87 �� 0.01, P increases in ACE2 protein and activity were accompanied by a significant increase in cardiac ACE2 mRNA expression (Fig. 1C, P= 0.05). The total ventricular collagen content was evaluated by the hydroxyproline assay method. Chronic administration of XNT (260 ng kg?1 min?1 for 28 days) considerably decreased (by approximately 15%) the total collagen content in the hearts of SHRs (Fig. 2, P Alisertib solubility dmso effect of XNT may be associated with increased cardiac ACE2 activity and levels. To evaluate the effects of XNT on ACE2 and Ang-(1�C7) expression in cardiac fibroblasts, the main cellular type involved in collagen deposition, we performed immunohistochemical analysis using histological sections from left ventricles of SHRs. We found that XNT treatment increased ACE2 expression by approximately 16% (P > 0.05) in both interstitial (Fig. 3B) and perivascular fibroblasts (Fig. 3D). In addition, similar effects were GSK J4 price observed ErbB for Ang-(1�C7) expression, i.e. the expression of Ang-(1�C7) was increased by about 16% (P > 0.05) in interstitial and perivascular fibroblasts of XNT-treated SHRs (Fig. 4B and D). To confirm these data, we incubated isolated fibroblasts with XNT. In keeping with our immunohistochemical results, isolated fibroblasts treated with XNT also exhibited higher expression of both ACE2 (Fig. 3G) and Ang-(1�C7) (Fig. 4G). It has been well established that ERK activation is one of the downstream signalling events that participates in collagen synthesis. Therefore, we examined whether the beneficial antifibrotic effect of XNT involved ERKs. As shown in Fig. 5A and B, phosphorylation of ERKs (p44 and p42) was higher in SHRs compared with WKY rats. Treatment with XNT restored or even reduced ERK phosphorylation in SHRs (phospho-ERK/total ERK ratio: WKY, 1.00 �� 0.04; control SHRs, 1.46 �� 0.25; treated SHRs, 0.86 �� 0.02, P