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Updated: Aug 11, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Interstitial fibroblast-like cells express renin-angiotensin system components in a fibrosing murine kidney
Hirokazu Okada1, Tsutomu Inoue, Yoshihiko Kanno
1Department of Nephrology, Saitama Medical College, Saitama, Japan.
Abstract:
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.
Insights
The renin-angiotensin system (RAS) plays a role in kidney fibrosis. Researchers found RAS components in tubular and interstitial cells of fibrosing kidneys, linking RAS to renal fibrogenesis.
Area of Science:
- Nephrology
- Renal Pathophysiology
- Molecular Biology
Background:
- The renin-angiotensin system (RAS) is increasingly recognized for its role in organ fibrosis.
- Limited information exists on the specific localization of RAS components within the fibrosing kidney.
Purpose of the Study:
- To investigate the localization of key renin-angiotensin system components in a murine model of renal fibrosis.
- To elucidate the spatial relationship between RAS elements and fibrotic changes in the kidney.
Main Methods:
- Utilized a murine model of renal fibrosis.
- Employed immunohistochemistry and in situ hybridization to detect angiotensin II receptors (AT(1A)R, AT(2)R), renin (REN), angiotensinogen (AGTN), and angiotensin-converting enzyme (ACE).
- Characterized interstitial fibroblast-like cells for vimentin and transforming growth factor-beta1 expression.
Main Results:
- Angiotensin II type 1A receptor (AT(1A)R) and angiotensinogen (AGTN) expression were enhanced in the fibrosing kidney model.
- Angiotensin II type 2 receptor (AT(2)R) and angiotensin-converting enzyme (ACE) expression were attenuated, while renin (REN) expression remained unchanged.
- RAS components were detected in both tubular epithelial cells and interstitial fibroblast-like cells.
- Interstitial fibroblast-like cells expressing AT(1A)R mRNA also expressed vimentin and transforming growth factor-beta1.
Conclusions:
- Demonstrated a tubulointerstitial renin-angiotensin system within the fibrosing kidney.
- Provided evidence for a direct link between the renin-angiotensin system and the process of renal fibrogenesis.
