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Association of Retinoic Acid Receptors with Extracellular Matrix Accumulation in Rats with Renal Interstitial Fibrosis Disease
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
* Author to whom correspondence should be addressed.
Received: 7 September 2012; in revised form: 24 October 2012 / Accepted: 25 October 2012 / Published: 31 October 2012
Abstract: The nuclear retinoic acid receptors (RARs) function as ligand-dependent transcriptional regulators and include three subtypes (RARα, RARβ and RARγ), which control the expression of specific gene subsets subsequent to ligand binding and to strictly controlled phosphorylation processes. Extracellular matrix (ECM) accumulation is the most important characteristic of renal interstitial fibrosis (RIF). This study was performed to investigate whether RARs were associated with ECM accumulation in the progression of RIF in rats. Eighty Wistar male rats were divided into a sham operation group (SHO) and a model group subjected to unilateral ureteral obstruction (GU) at random; n = 40, respectively. The RIF disease in GU group was established by left ureteral ligation. The renal tissues were collected at two weeks and four weeks after surgery. Protein expressions of RARα, RARβ, RARγ, transforming growth factor-βl (TGF-β1), collagen-IV (Col-IV) and fibronectin (FN) were detected using immunohistochemical analysis, and mRNA expressions of RARα, RARβ, RARγ and TGF-β1 in renal tissue were detected by real time reverse transcription polymerase chain reaction. RIF index in renal interstitium was also calculated. When compared with those in SHO group, expressions of RARα and RARβ (protein and mRNA) were markedly reduced in the GU group (each p < 0.01). There was no marked difference for the expression of RARγ (protein and mRNA) between the SHO group and the GU group. The expressions of TGF-β1, Col-IV, FN and the RIF index in the GU group were markedly increased when compared with those in the SHO group (each p < 0.01). The protein expression of RARα/RARβ was negatively correlated with protein expression of TGF-β1, Col-IV or FN and the RIF index (all p < 0.01). In conclusion, the low expression of RARα/RARβ is associated with ECM accumulation in the progression of RIF in rats, suggesting that RARα/RARβ is a potentially therapeutic target for prevention of RIF.
Keywords: retinoic acid receptors; RARs; RARα; RARβ; RARγ; extracellular matrix; renal interstitial fibrosis
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MDPI and ACS Style
Long, Y.-B.; Qin, Y.-H.; Zhou, T.-B.; Lei, F.-Y. Association of Retinoic Acid Receptors with Extracellular Matrix Accumulation in Rats with Renal Interstitial Fibrosis Disease. Int. J. Mol. Sci. 2012, 13, 14073-14085.
Long Y-B, Qin Y-H, Zhou T-B, Lei F-Y. Association of Retinoic Acid Receptors with Extracellular Matrix Accumulation in Rats with Renal Interstitial Fibrosis Disease. International Journal of Molecular Sciences. 2012; 13(11):14073-14085.
Long, Yao-Bin; Qin, Yuan-Han; Zhou, Tian-Biao; Lei, Feng-Ying. 2012. "Association of Retinoic Acid Receptors with Extracellular Matrix Accumulation in Rats with Renal Interstitial Fibrosis Disease." Int. J. Mol. Sci. 13, no. 11: 14073-14085.