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Baicalin attenuates adriamycin-induced nephrotic syndrome by regulating fibrosis procession and inflammatory reaction

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Abstract

Background

Baicalin has anti-inflammatory, antibacterial, blood platelet aggregation-inhibiting, free oxygen radical-clearing, and endotoxin-decreasing properties. However, its molecular mechanism involved in the treatment of Adriamycin-induced nephrotic syndrome (NS) is still unclear.

Objective

This study aimed to explore the effects of baicalin on Adriamycin-induced nephrotic syndrome (NS) and to characterize the genes involved in this progression.

Methods

We established Adriamycin-induced NS model in 32 rats and used six rats in Sham group. Urinary total protein content and creatinine serum were assessed as physiological indicators. H&E staining was used to observe the pathological changes. We determined gene expression profiles using transcriptome sequencing in the rat kidney tissues from Sham, Adriamycin, and Adriamycin + baicalin groups. KEGG was carried out to analyze the enriched pathways of differentially expressed genes among these groups.

Results

Baicalin treatment relieved renal injury in NS rats. Expression of 363 genes was significantly different between the Adriamycin and Adriamycin + baicalin M groups. Most of the differentially expressed genes were enriched in pathways involved in epithelial-mesenchymal transition (EMT), fibrosis, apoptosis, and inflammation.

Conclusions

Overall, these data suggest that Adriamycin-induced NS can be attenuated by baicalin through the suppression of fibrosis-related genes and inflammatory reactions. Baicalin is a potential drug candidate for the treatment of NS, and the identified genes represent potential therapeutic targets.

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References

  • Adams JC, Lawler J (2011) The thrombospondins. Cold Spring Harb Perspect Biol 3:a009712

    Article  Google Scholar 

  • Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y, Mecca G, Remuzzi G, Donati MB (1982) Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. Lab Investig 46:16–23

    CAS  PubMed  Google Scholar 

  • Bhattacharyya S, Wang WX, Morales-Nebreda L, Feng G, Wu MH, Zhou XD, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C et al (2016) Tenascin-C drives persistence of organ fibrosis. Nat Commun 7:11703

    Article  CAS  Google Scholar 

  • Carvajal G, Rodriguez-Vita J, Rodrigues-Diez R, Sanchez-Lopez E, Ruperez M, Cartier C, Esteban V, Ortiz A, Egido J, Mezzano SA et al (2008) Angiotensin II activates the Smad pathway during epithelial mesenchymal transdifferentiation. Kidney Int 74:585–595

    Article  CAS  Google Scholar 

  • Chan SC, Zhang Y, Shao AN, Avdulov S, Herrera J, Aboudehen K, Pontoglio M, Igarashi P (2018) Mechanism of fibrosis in HNF1B-related autosomal dominant tubulointerstitial kidney disease. J Am Soc Nephrol 29:2493–2509

    Article  CAS  Google Scholar 

  • D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411

    Article  Google Scholar 

  • Daniel C, Wiede J, Krutzsch HC, Ribeiro SMF, Roberts DD, Murphy-Ullrich JE, Hugo C (2004) Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo. Kidney Int 65:459–468

    Article  CAS  Google Scholar 

  • Franco HL, Casasnovas J, Rodriguez-Medina JR, Cadilla CL (2011) Redundant or separate entities?-roles of Twist1 and Twist2 as molecular switches during gene transcription. Nucleic Acids Res 39:1177–1186

    Article  CAS  Google Scholar 

  • Fu HY, Tian Y, Zhou LL, Zhou D, Tan RJ, Stolz DB, Liu YH (2017) Tenascin-C is a major component of the fibrogenic niche in kidney fibrosis. J Am Soc Nephrol 28:785–801

    Article  CAS  Google Scholar 

  • Hu ZB, Ma KL, Zhang Y, Wang GH, Liu L, Lu J, Chen PP, Lu CC, Liu BC (2018) Inflammation-activated CXCL16 pathway contributes to tubulointerstitial injury in mouse diabetic nephropathy. Acta Pharmacol Sin 39:1022–1033

    Article  CAS  Google Scholar 

  • Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Investig 119:1420–1428

    Article  CAS  Google Scholar 

  • Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45:D353–D361

    Article  CAS  Google Scholar 

  • Kerlin BA, Ayoob R, Smoyer WE (2012) Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol 7:513–520

    Article  CAS  Google Scholar 

  • Kim DH, Kim JM, Lee EK, Choi YJ, Kim CH, Choi JS, Kim ND, Yu BP, Chung HY (2012) Modulation of FoxO1 phosphorylation/acetylation by baicalin during aging. J Nutr Biochem 23:1277–1284

    Article  CAS  Google Scholar 

  • Li H, Hu J, Ma L, Yuan Z, Wang Y, Wang X, Xing D, Lei F, Du L (2010) Comprehensive study of baicalin down-regulating NOD2 receptor expression of neurons with oxygen-glucose deprivation in vitro and cerebral ischemia-reperfusion in vivo. Eur J Pharmacol 649:92–99

    Article  CAS  Google Scholar 

  • Liang S, Li Q, Zhu HY, Zhou JH, Ding R, Chen XM, Cai GY (2014) Clinical factors associated with the diagnosis and progression of diabetic nephropathy. Cell Biochem Biophys 70:9–15

    Article  CAS  Google Scholar 

  • Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A (2004) Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development 131:3401–3410

    Article  CAS  Google Scholar 

  • Murphy-Ullrich JE (2019) Thrombospondin 1 and its diverse roles as a regulator of extracellular matrix in fibrotic disease. J Histochem Cytochem 67:683–699

    Article  CAS  Google Scholar 

  • Murphy-Ullrich JE, Sage EH (2014) Revisiting the matricellular concept. Matrix Biol 37:1–14

    Article  CAS  Google Scholar 

  • Nechemia-Arbely Y, Barkan D, Pizov G, Shriki A, Rose-John S, Galun E, Axelrod JH (2008) IL-6/IL-6R axis plays a critical role in acute kidney injury. J Am Soc Nephrol 19:1106–1115

    Article  CAS  Google Scholar 

  • Peters M, Muller AM, Rose-John S (1998) Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92:3495–3504

    Article  CAS  Google Scholar 

  • Rashikh A, Pillai KK, Ahmad SJ, Akhtar M, Najmi AK (2013) Aliskiren alleviates doxorubicin-induced nephrotoxicity by inhibiting oxidative stress and podocyte injury. J Renin Angiotensin Aldosterone Syst 14:14–22

    Article  Google Scholar 

  • Rodrigues-Diez R, Rodrigues-Diez RR, Lavoz C, Carvajal G, Droguett A, Garcia-Redondo AB, Rodriguez I, Ortiz A, Egido J, Mezzano S et al (2014) Gremlin activates the Smad pathway linked to epithelial mesenchymal transdifferentiation in cultured tubular epithelial cells. Biomed Res Int 2014:802841

    Article  Google Scholar 

  • Roxburgh SA, Murphy M, Pollock CA, Brazil DP (2006) Recapitulation of embryological programmes in renal fibrosis–the importance of epithelial cell plasticity and developmental genes. Nephron Physiol 103:p139-148

    Article  Google Scholar 

  • Tober J, Maijenburg MW, Speck NA (2016) Taking the leap: Runx1 in the formation of blood from endothelium. Hematopoiesis 118:113–162

    Article  CAS  Google Scholar 

  • Tucker RP, Chiquet-Ehrismann R (2015) Tenascin-C: its functions as an integrin ligand. Int J Biochem Cell Biol 65:165–168

    Article  CAS  Google Scholar 

  • Wang Y, Wang Y, Feng X, Bao S, Yi S, Kairaitis L, Tay YC, Rangan GK, Harris DC (2001) Depletion of CD4(+) T cells aggravates glomerular and interstitial injury in murine adriamycin nephropathy. Kidney Int 59:975–984

    Article  CAS  Google Scholar 

  • Wang G, Liang J, Gao LR, Si ZP, Zhang XT, Liang G, Yan Y, Li K, Cheng X, Bao Y et al (2018) Baicalin administration attenuates hyperglycemia-induced malformation of cardiovascular system. Cell Death Dis 9:234

    Article  CAS  Google Scholar 

  • Xiao Y, Ye J, Zhou Y, Huang J, Liu X, Huang B, Zhu L, Wu B, Zhang G, Cai Y (2018) Baicalin inhibits pressure overload-induced cardiac fibrosis through regulating AMPK/TGF-beta/Smads signaling pathway. Arch Biochem Biophys 640:37–46

    Article  CAS  Google Scholar 

  • Xiping Z, Jie Z, Qin X, Guanghua F, Yang C, Tongfa J, Qi X (2009) Influence of baicalin and octreotide on NF-kappaB and p-selectin expression in liver and kidney of rats with severe acute pancreatitis. Inflammation 32:1–11

    Article  Google Scholar 

  • Yap ML, Wang X, Pietersz GA, Peter K (2018) Mesoscale nanoparticles: an unexpected means for selective therapeutic targeting of kidney diseases! Hypertension 71:61–63

    Article  CAS  Google Scholar 

  • Yiu WH, Lin M, Tang SCW (2014) Toll-like receptor activation: from renal inflammation to fibrosis. Kidney Int Suppl 4:20–25

    Article  CAS  Google Scholar 

  • Zhang Q, Shi Y, Wada J, Malakauskas SM, Liu M, Ren Y, Du C, Duan H, Li Y, Li Y et al (2010) In vivo delivery of Gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7. PLoS ONE 5:e11709

    Article  Google Scholar 

  • Zhang M, Guo Y, Fu H, Hu S, Pan J, Wang Y, Cheng J, Song J, Yu Q, Zhang S et al (2015) Chop deficiency prevents UUO-induced renal fibrosis by attenuating fibrotic signals originated from Hmgb1/TLR4/NF kappa B/IL-1 beta signaling. Cell Death Dis 6:e1847

    Article  CAS  Google Scholar 

  • Zhang Q, Ye Q, Huang X, Xu A, Liu Y, Qi J, Zhang H, Zhang J (2020) Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy. BMC Complement Med Ther 20:362

    Article  Google Scholar 

  • Zhou T, Luo MC, Cai W, Zhou SY, Feng DY, Xu CD, Wang HY (2018) Runt-related transcription factor 1 (RUNX1) promotes TGF-beta-induced renal tubular epithelial-to-mesenchymal transition (EMT) and renal fibrosis through the PI3K subunit p110 delta. EBioMedicine 31:217–225

    Article  Google Scholar 

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Funding

This work was supported by the [Guangdong Science and Technology Research Project] under Grant [Number 2017A020215129]; [Shenzhen Scientific Techology Basic Research Projects] under Grant [Number JCYJ20160429183052202]; [Shenzhen Health and Family Planning Research Project] under Grant [Number 201606050]; and [Shenzhen Nanshan District Scientific Research Project] under Grant [Number 2015021].

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Authors and Affiliations

  1. Traditional Chinese Medicine Department of Rheumatism, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), 89 Taoyuan Road, Nanshan District, Shenzhen, 518052, Guangdong, China

    Ning Tan, Chen-Xia Sun, Hui-Jun Zhu, De-Yu Li, Sheng-Guang Huang & Shou-Di He

Authors
  1. Ning Tan
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  2. Chen-Xia Sun
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  3. Hui-Jun Zhu
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  4. De-Yu Li
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  5. Sheng-Guang Huang
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  6. Shou-Di He
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Contributions

NT and S-DH made substantial contributions to the conception or design of the manuscript. NT, C-XS, H-JZ, D-YL, S-GH, and S-DH participated in the completion of the experiment. All authors were involved in drafting the manuscript or revising it critically for important intellectual content. All author gave final approval of manuscript and were accountable for all aspects of the work in ensuring the accuracy and integrity of this manuscript.

Corresponding author

Correspondence to Shou-Di He.

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Conflict of interest

Ning Tan, Chen-Xia Sun, Hui-Jun Zhu, De-Yu Li, Sheng-Guang Huang, and Shou-Di He declare that they have no conflict of interest.

Ethical approval

All experimental procedures performed on SD rats were approved by Traditional Chinese Medicine Department of Rheumatism, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital).

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Tan, N., Sun, CX., Zhu, HJ. et al. Baicalin attenuates adriamycin-induced nephrotic syndrome by regulating fibrosis procession and inflammatory reaction. Genes Genom 43, 1011–1021 (2021). https://doi.org/10.1007/s13258-021-01107-x

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  • DOI: https://doi.org/10.1007/s13258-021-01107-x

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