BIOLOGICAL FUNCTION OF ANGIOTENSIN IN MACROPHAGES

Vanderbilt University, Nashville TN

Investigators

Linked publications & trials

Abstract

Description (provided by applicant) It is now clear that angiotensin II (Ang II) has a significant role in the process of renal scarring. Over the last two decades, there has been ample clinical and experimental support for a detrimental effect of Ang II type 1 receptor (Agtr1) on intrinsic renal cells that contributes to scarring. Recent in vitro studies strongly suggested that functional Agtr1 is expressed in bone marrow-derived circulating cells, including macrophages. However, due to technical obstacles, the in vivo function of the Agtr1 in macrophages, specifically, has not been fully investigated. In this regard, the technique of transplantation genetically engineered hematopoietic stem cells has recently been established as a useful tool to examine the role of molecules expressed by bone marrow-derived macrophages in vivo. The Principal Investigator (PI) applied the technique to identify the role of the renin-angiotensin system within bone marrow-derived cells in renal tissue scarring processes in vivo. When the bone marrow from Agtr1-/- mice is transplanted into Agtr1 +/+ wild type mice, it was repetitively shown that accumulation of macrophages in the kidney, which should typically been seen during obstructive insult, is hindered. Interestingly, renal interstitial fibrosis is developed in an accelerated manner. These data indicate that the protective role of macrophage Agtr1 in renal tissue scaring is surprising in view of the current prevailing notion that both Agtr1 and macrophages promote scaring. These observations constitute the basis of the current proposal, which is geared to clarifying the underlying mechanisms for the possible beneficial role of the macrophage Agtr1 in renal tissue injury. These studies reveal that the hematopoetic stem cell is a reasonable target for the therapeutic intervention of renal diseases.