Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

Abstract

Aim: Both adrenomedullin (ADM) and adrenotensin (ADT) are derived from the same propeptide precursor, and both act as circulating hormones and local paracrine mediators with multiple biological activities. Compared with ADM, little is known about how ADT achieves its functions. In the present study, we investigated the effect of ADT on cell proliferation and transforming growth factor-β (TGF-β) secretion in cultured renal mesangial cells (MCs) and determined whether angiotensin II (Ang II) was involved in mediating this process. Methods: Cell proliferation was measured by bromodeoxyuridine (BrdU) incorporation assay, Ang II levels were assayed using an enzyme immunoassay, and real time PCR was used to measure Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, angiotensinogen (AGT), renin, angiotensin converting enzyme (ACE) and TGF-β1 mRNA levels. TGF-β1 and collagen type IV protein levels in cell media were measured using enzyme-linked immunoassays. Results: ADT treatment induced cell proliferation in a concentration-dependent manner; it also increased the levels of TGF-β1 mRNA and protein as well as collagen type IV excretion by cultured MCs. ADT treatment increased renin and AGT mRNAs as well as Ang II protein, but did not affect the ACE mRNA level. ADT up-regulated angiotensin AT1 receptor mRNA, but not that of the AT2 receptor. The angiotensin AT1 receptor antagonist losartan blocked the effects of ADT-induced cell proliferation, TGF-β1 and collagen type IV synthesis and secretion. Conclusion: ADT has a stimulating role in cell proliferation in cultured MCs. Increases in the levels of Ang II and the AT1 receptor after ADT treatment mediate the stimulating effects of ADT on cell proliferation and extracellular matrix synthesis and secretion.

Enhanced angiotensin-converting enzyme 2 attenuates angiotensin II-induced collagen production via AT1 receptor–phosphoinositide 3-kinase–Akt pathway

“…In this study, our results reveal the signaling events that First, unlike other published reports [8,33,34], Ang II induced the mRNA synthesis of neither type III nor type IV, but type I collagens in mesangial cells. Second, Ang II, via AT-1R, increased collagen synthesis through transactivation of the PI3K signaling pathway.…”

A novel angiogenic peptide, ΔADT: A truncated adrenotensin peptide revealed by secretory peptidome analysis of human retinal pericytes

“…This result indicates that ADT and ΔADT are able to stimulate the proliferation of endothelial cells, and suggests that ΔADT has a higher proliferation rate than ADT. In addition, this finding is consistent with reports showing the effects of ADT on upregulated proliferation in rat mesangial cells and pulmonary arterial smooth muscle cells (19,20).…”

Angiotensin AT1 receptor activation mediates high glucose‐induced epithelial–mesenchymal transition in renal proximal tubular cells

“…Angiotensin II secreted by cultured NRK‐52E cells was measured using an enzyme immunoassay‐based colorimetric kit (Phoenix Pharmaceuticals, Burlingame, CA, USA) 20 . Briefly, samples were added to a secondary antibody‐precoated immunoplate.…”