Absence of angiotensin II type 1 receptor in bone marrow–derived cells is detrimental in the evolution of renal fibrosis

Unexpected news in renal fibrosis

“…The mechanism(s) whereby macrophages may facilitate renal fibrogenesis is undefined, and the myriad functions of which macrophages appear to be capable suggest that their role in this process may well be very complex. Indeed, in this issue of the JCI, Nishida et al (11) present evidence that infiltrating macrophages in the kidney may play a beneficial antifibrotic role that, surprisingly, requires the action of angiotensin.…”

“…Nishida et al (11) consider other possibilities by which invading macrophages could inhibit renal fibrosis. Macrophages can be a source of HGF (16), recently found to block the conversion of renal epithelia to mesenchymal cells (17,18).…”

Unexpected news in renal fibrosis

“…However, the consequences of disrupting angiotensin II activity, given its vast array of cell targets, are likely to be many, and evidence exists that the renin-angiotensin system can directly regulate macrophage function (14,15). To more precisely examine the role of infiltrating macrophages in renal fibrogenesis, Nishida et al (11) used wild-type mice that were transplanted, after lethal irradiation, with bone marrow from mice lacking the Agtr1a gene. Unexpectedly, 2 weeks after UUO, kidneys from mice with Agtr1-deficient bone marrow showed more renal fibrosis and less infiltrating macrophages than did those from wildtype mice.…”

“…Given the myriad actions described for these cells, the possibilities are many, but it could simply be due to their ability to phagocytize dead cells and cellular debris. Indeed, analysis of macrophage function by Nishida et al (11) revealed that macrophages lacking Agtr1a have reduced migratory capacity and decreased phagocytic activity, a characteristic that could also be elicited in wild-type macrophages by the angiotensin II receptor antagonist losartan. Since inhibitors of the renin-angiotensin system are widely used in clinical medicine, it is urgently important to determine whether they block beneficial effects of invading macrophages.…”

“…Furthermore, bone marrow also contains mesenchymal stem cells that might migrate to disease organs and participate in tissue repair (24). Regardless of the mechanism whereby invading macrophages (and/or other bone marrow cells) exert their antifibrotic effect, Nishida et al (11) cast a new light on the role of macrophages in renal fibrosis and, more importantly, call attention to possible interactions between bone marrow cells and the kidney. Indeed, the kidneys of rats transplanted with bone marrow expressing green fluorescent protein (GFP) show a surprising abundance of interstitial GFP-positive cells (25), further supporting the notion that bone marrow cells play important and unexpected roles in renal regulation and disease.…”