Effects of Huangkui Capsule on the Expression of SPARC in the Kidney Tissue of a Rat Model with Diabetic Nephropathy

Author(s): Xiaoyao Yang, Meng Luo, Qinghua Jiang*, Yiwei Wang*.

Journal Name: Current Gene Therapy

Volume 19 , Issue 4 , 2019

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Graphical Abstract:


Abstract:

Objective: The objective of the research is to investigate the effects of Huangkui capsule on the expression of SPARC in the kidney tissues of diabetic nephropathy.

Methods: SD rats were divided into three groups: normal control group, untreated DN group and HKC-treated DN group. The therapeutic effects and underlying molecular mechanism of HKC on DN rats induced by streptozotocin were evaluated by the levels of serum creatinine, blood urea nitrogen, 24-hour urinary protein and the expression of SPARC. Pathological changes in kidney tissues were observed through hematoxylin-eosin (HE) staining. Moreover, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the variation of SPARC.

Results: This study was performed to investigate the effects of HKC on DN in SD rats model and its molecular mechanism. Our results showed that the rats treated with HKC had an improved general state and reduced creatinine, blood urea nitrogen and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with HKC. HE staining was utilized to observe that HKC can improve histopathological findings in the kidney tissues of DN rats, including kidney fibrosis. Results of western blot and qRT-PCR showed that HKC can inhibit the expressions of SPARC in the rat model of DN.

Conclusion: The present findings demonstrated that HKC inhibited SPARC level and had significant therapeutic effects on DN.

Keywords: Huangkui capsule, diabetic nephropathy, SPARC, diabetes, TCMs, renal function.

[1]
Adeshara KA, Diwan AG, Tupe RS. Diabetes and complications: Cellular signaling pathways, current understanding and targeted therapies. Curr Drug Targets 2016; 17(11): 1309-28.
[http://dx.doi.org/10.2174/1389450117666151209124007] [PMID: 26648059]
[2]
Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 2003; 348(25): 2543-56.
[http://dx.doi.org/10.1056/NEJMra022296] [PMID: 12815141]
[3]
Cheng L, Wang P, Tian R, et al. LncRNA2Target v2.0: A comprehensive database for target genes of lncRNAs in human and mouse. Nucleic Acids Res 2019; 47(D1): D140-4.
[http://dx.doi.org/10.1093/nar/gky1051] [PMID: 30380072]
[4]
Cheng L, Hu Y, Sun J, Zhou M, Jiang Q. DincRNA: A comprehensive web-based bioinformatics toolkit for exploring disease associations and ncRNA function. Bioinformatics 2018; 34(11): 1953-6.
[http://dx.doi.org/10.1093/bioinformatics/bty002] [PMID: 29365045]
[5]
Lane TF, Sage EH. The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB J 1994; 8(2): 163-73.
[http://dx.doi.org/10.1096/fasebj.8.2.8119487] [PMID: 8119487]
[6]
Jørgensen LH, Jepsen PL, Boysen A, et al. SPARC Interacts with actin in skeletal muscle in vitro and in vivo. Am J Pathol 2017; 187(2): 457-74.
[http://dx.doi.org/10.1016/j.ajpath.2016.10.013] [PMID: 27908613]
[7]
Camino AM, Atorrasagasti C, Maccio D, et al. Adenovirus-mediated inhibition of SPARC attenuates liver fibrosis in rats. J Gene Med 2008; 10(9): 993-1004.
[http://dx.doi.org/10.1002/jgm.1228] [PMID: 18615449]
[8]
Wong SL, Sukkar MB. The SPARC protein: An overview of its role in lung cancer and pulmonary fibrosis and its potential role in chronic airways disease. Br J Pharmacol 2017; 174(1): 3-14.
[http://dx.doi.org/10.1111/bph.13653] [PMID: 27759879]
[9]
Kos K, Wong S, Tan B, et al. Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose. Diabetes 2009; 58(8): 1780-8.
[http://dx.doi.org/10.2337/db09-0211] [PMID: 19509023]
[10]
Takahashi M, Nagaretani H, Funahashi T, et al. The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease. Obes Res 2001; 9(7): 388-93.
[http://dx.doi.org/10.1038/oby.2001.50] [PMID: 11445660]
[11]
Tseng C, Kolonin MG. Proteolytic isoforms of SPARC induce adipose stromal cell mobilization in obesity. Stem Cells 2016; 34(1): 174-90.
[http://dx.doi.org/10.1002/stem.2192] [PMID: 26381424]
[12]
Li P, Chen YZ, Lin HL, et al. Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: Study protocol for a randomized controlled trial. Trials 2017; 18(1): 170.
[http://dx.doi.org/10.1186/s13063-016-1774-6] [PMID: 28395659]
[13]
Ge J, Miao JJ, Sun XY, Yu JY. Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator-activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. J Ethnopharmacol 2016; 189: 238-49.
[http://dx.doi.org/10.1016/j.jep.2016.05.033] [PMID: 27224243]
[14]
Mao ZM, Shen SM, Wan YG, et al. Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid. J Ethnopharmacol 2015; 173: 256-65.
[http://dx.doi.org/10.1016/j.jep.2015.07.036] [PMID: 26226437]
[15]
Cai HD, Su SL, Qian DW, et al. Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids. J Ethnopharmacol 2017; 206: 152-9.
[http://dx.doi.org/10.1016/j.jep.2017.02.046] [PMID: 28408246]
[16]
Maezawa Y, Yokote K, Sonezaki K, et al. Influence of C-peptide on early glomerular changes in diabetic mice. Diabetes Metab Res Rev 2006; 22(4): 313-22.
[http://dx.doi.org/10.1002/dmrr.612] [PMID: 16389646]
[17]
Liu X, Liu L, Chen P, et al. Clinical trials of traditional Chinese medicine in the treatment of diabetic nephropathy--a systematic review based on a subgroup analysis. J Ethnopharmacol 2014; 151(2): 810-9.
[http://dx.doi.org/10.1016/j.jep.2013.11.028] [PMID: 24296085]
[18]
Zhuang Q, Cheng K, Ming Y. CX3CL1/CX3CR1 axis, as the therapeutic potential in renal diseases: Friend or foe. Curr Gene Ther 2017; 17(6): 442-52.
[http://dx.doi.org/10.2174/1566523218666180214092536] [PMID: 29446734]
[19]
Yang X, Mou S. Role of immune cells in diabetic kidney disease. Curr Gene Ther 2017; 17(6): 424-33.
[http://dx.doi.org/10.2174/1566523218666180214100351] [PMID: 29446740]
[20]
Taneda S, Pippin JW, Sage EH, et al. Amelioration of diabetic nephropathy in SPARC-null mice. J Am Soc Nephrol 2003; 14(4): 968-80.
[http://dx.doi.org/10.1097/01.ASN.0000054498.83125.90] [PMID: 12660331]
[21]
Socha MJ, Manhiani M, Said N, Imig JD, Motamed K. Secreted protein acidic and rich in cysteine deficiency ameliorates renal inflammation and fibrosis in angiotensin hypertension. Am J Pathol 2007; 171(4): 1104-12.
[http://dx.doi.org/10.2353/ajpath.2007.061273] [PMID: 17717147]
[22]
Gilbert RE, McNally PG, Cox A, et al. SPARC gene expression is reduced in early diabetes-related kidney growth. Kidney Int 1995; 48(4): 1216-25.
[http://dx.doi.org/10.1038/ki.1995.405] [PMID: 8569083]
[23]
Munjal ID, McLean NV, Grant MB, Blake DA. Differences in the synthesis of secreted proteins in human retinal endothelial cells of diabetic and nondiabetic origin. Curr Eye Res 1994; 13(4): 303-10.
[http://dx.doi.org/10.3109/02713689408995792] [PMID: 8033591]
[24]
Jandeleit-Dahm K, Rumble J, Cox AJ, et al. SPARC gene expression is increased in diabetes-related mesenteric vascular hypertrophy. Microvasc Res 2000; 59(1): 61-71.
[http://dx.doi.org/10.1006/mvre.1999.2189] [PMID: 10625572]
[25]
Wang Z, Song HY, An MM, Zhu LL. Association of serum SPARC level with severity of coronary artery lesion in type 2 diabetic patients with coronary heart disease. Int J Clin Exp Med 2015; 8(10): 19290-6.
[PMID: 26770566]
[26]
Xin C, Xia Z, Jiang C, Lin M, Li G. Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling. Drug Des Devel Ther 2015; 9: 6269-74.
[http://dx.doi.org/10.2147/DDDT.S93964] [PMID: 26664048]
[27]
Han H, Cao A, Wang L, et al. Huangqi decoction ameliorates streptozotocin-induced rat diabetic nephropathy through antioxidant and regulation of the TGF-β/MAPK/PPAR-γ signaling. Cell Physiol Biochem 2017; 42(5): 1934-44.
[http://dx.doi.org/10.1159/000479834] [PMID: 28793292]
[28]
Zhang N, Gao Y, Zou D, et al. Effects of chinese medicine tong xinluo on diabetic nephropathy via inhibiting TGF- β 1-Induced epithelial-to-mesenchymal transition. Evid Based Complement Alternat Med 2014; 2014123497
[http://dx.doi.org/10.1155/2014/123497] [PMID: 24864150]


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Article Details

VOLUME: 19
ISSUE: 4
Year: 2019
Page: [211 - 215]
Pages: 5
DOI: 10.2174/1566523219666190925112249
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