Interstitial fibroblast-like cells express renin-angiotensin system components in a fibrosing murine kidney.
Recently, the renin-angiotensin system (RAS) was implicated in organ fibrosis. However, few studies have examined the localization of RAS components, such as angiotensin II receptors, renin (REN), angiotensinogen (AGTN), and angiotensin-converting enzyme (ACE), in the fibrosing kidney. To localize these components in the fibrosing kidney, we used a murine model of renal fibrosis that shows an enhanced expression of angiotensin II type 1A receptor (AT(1A)R) and AGTN. Our results indicate that the overall expression of angiotensin II type 2 receptor (AT(2)R) and ACE was attenuated in this model, whereas REN expression was unchanged. In addition to tubular epithelial cells that were positive for AT(1A)R, AT(2)R, REN, and AGTN, interstitial fibroblast-like cells expressed AT(1A)R, REN, AGTN, and ACE in the fibrosing kidney. The interstitial fibroblast-like cells that were positive for AT(1A)R mRNA were further characterized as positive for the expression of vimentin and transforming growth factor-beta1. These data provide strong evidence for a tubulointerstitial RAS within the fibrosing kidney, and a linkage between the RAS and renal fibrogenesis.
Okada
Hirokazu
H
Department of Nephrology, Saitama Medical College, Saitama, Japan.
Inoue
Tsutomu
T
Kanno
Yoshihiko
Y
Kobayashi
Tatsuya
T
Watanabe
Yusuke
Y
Kopp
Jeffrey B
JB
Carey
Robert M
RM
Suzuki
Hiromichi
H
D000818:Animals; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D012084:Renin-Angiotensin System