SAMiRNA Targeting Amphiregulin Alleviate Total-Body-Irradiation-Induced Renal Fibrosis.

Beomseok Son, Tae Rim Kim, Jun Hong Park, Sung-Il Yun, Hanjoo Choi, Ji Woo Choi, ChanHyeok Jeon, Han-Oh Park

Radiation research 2022 May 01

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Fibrosis is a serious unintended side effect of radiation therapy. In this study, we aimed to investigate whether amphiregulin (AREG) plays a critical role in fibrosis development after total-body irradiation (TBI). We found that the expression of AREG and fibrotic markers, such as α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1α1), was elevated in the kidneys of 6 Gy TBI mice. Expression of AREG and α-SMA was mainly elevated in the proximal and distal tubules of the kidney in response to TBI, which was confirmed by immunofluorescence staining. Knockdown of Areg mRNA using self-assembled-micelle inhibitory RNA (SAMiRNA) significantly reduced the expression of fibrotic markers, including α-SMA and COL1α1, and inflammatory regulators. Finally, intravenous injections of SAMiRNA targeting mouse Areg mRNA (SAMiRNA-mAREG) diminished radiation-induced collagen accumulation in the renal cortex and medulla. Taken together, the results of the present study suggest that blocking of AREG signaling via SAMiRNA-mAREG treatment could be a promising therapeutic approach to alleviate radiation-induced kidney fibrosis. ©2022 by Radiation Research Society. All rights of reproduction in any form reserved.

Citation

Beomseok Son, Tae Rim Kim, Jun Hong Park, Sung-Il Yun, Hanjoo Choi, Ji Woo Choi, ChanHyeok Jeon, Han-Oh Park. SAMiRNA Targeting Amphiregulin Alleviate Total-Body-Irradiation-Induced Renal Fibrosis. Radiation research. 2022 May 01;197(5):471-479