Skip to main content
SpringerLink
Log in

Interference of S100A16 suppresses lipid accumulation and inflammation in high glucose-induced HK-2 cells

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Diabetic nephropathy (DN) is a major complication of diabetic mellitus and usually leads to the end-stage renal disease. Inflammation-induced lipid disorders have been proposed to play an important role in the pathogenesis of DN. S100A16 is a novel adipogenic factor, but has not been investigated in DN. This study aims to explore the role of S100A16 in high glucose (HG)-induced HK-2 cells.

Methods

CCK-8 assay was used to detect cell viability. Cell transfection was performed to knockdown S100A16. Oil red staining was performed to assay lipid accumulation. qRT-PCR and western blotting were conducted to examine corresponding gene expression. Intracellular cholesterol was determined by enzymatic assay. Inflammatory cytokines production was measured using ELISA kits.

Results

The results exhibited lipid accumulation and upregulation of S100A16 in HG-induced HK-2 cells. S100A16 knockdown significantly reduced lipid droplets and cholesterol, and decreased the production of inflammatory cytokines induced by HG. Besides, S100A16 knockdown decreased the expression of SCAP, SREBP1, SCD1 and SCAP. However, the inhibitory effect in HG-induced HK-2 cells made by S100A16 was reversed by SREBP1 overexpression.

Conclusion

These results suggested that S100A16 knockdown might protect against HG-induced lipid accumulation and inflammation in HK-2 cells through regulating SCAP/SREBP1 signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Lee JH, Kim D, Oh YS, Jun HS (2019) Lysophosphatidic acid signaling in diabetic nephropathy. Int J Mol Sci. https://doi.org/10.3390/ijms20112850

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kihm L (2016) Hypertension and diabetic nephropathy. Exp Clin Endocrinol Diabetes 124(6):333–334. https://doi.org/10.1055/s-0042-110231

    Article  CAS  PubMed  Google Scholar 

  3. Disease GBD, Injury I, Prevalence C (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392(10159):1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7

    Article  Google Scholar 

  4. Selby NM, Taal MW (2020) An updated overview of diabetic nephropathy: diagnosis, prognosis, treatment goals and latest guidelines. Diabetes Obes Metab 22(Suppl 1):3–15. https://doi.org/10.1111/dom.14007

    Article  PubMed  Google Scholar 

  5. Maezawa Y, Takemoto M, Yokote K (2015) Cell biology of diabetic nephropathy: roles of endothelial cells, tubulointerstitial cells and podocytes. J Diabetes Investig 6(1):3–15. https://doi.org/10.1111/jdi.12255

    Article  PubMed  Google Scholar 

  6. Zhang Y, Ma KL, Liu J, Wu Y, Hu ZB, Liu L, Lu J, Zhang XL, Liu BC (2015) Inflammatory stress exacerbates lipid accumulation and podocyte injuries in diabetic nephropathy. Acta Diabetol 52(6):1045–1056. https://doi.org/10.1007/s00592-015-0753-9

    Article  CAS  PubMed  Google Scholar 

  7. Wang XX, Jiang T, Shen Y, Adorini L, Pruzanski M, Gonzalez FJ, Scherzer P, Lewis L, Miyazaki-Anzai S, Levi M (2009) The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria. Am J Physiol Renal Physiol 297(6):F1587-1596. https://doi.org/10.1152/ajprenal.00404.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Herman-Edelstein M, Scherzer P, Tobar A, Levi M, Gafter U (2014) Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res 55(3):561–572. https://doi.org/10.1194/jlr.P040501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sakamoto A, Hongo M, Saito K, Nagai R, Ishizaka N (2012) Reduction of renal lipid content and proteinuria by a PPAR-gamma agonist in a rat model of angiotensin II-induced hypertension. Eur J Pharmacol 682(1–3):131–136. https://doi.org/10.1016/j.ejphar.2012.02.027

    Article  CAS  PubMed  Google Scholar 

  10. Marenholz I, Heizmann CW (2004) S100A16, a ubiquitously expressed EF-hand protein which is up-regulated in tumors. Biochem Biophys Res Commun 313(2):237–244. https://doi.org/10.1016/j.bbrc.2003.11.115

    Article  CAS  PubMed  Google Scholar 

  11. Liu Y, Zhang R, Xin J, Sun Y, Li J, Wei D, Zhao AZ (2011) Identification of S100A16 as a novel adipogenesis promoting factor in 3T3-L1 cells. Endocrinology 152(3):903–911. https://doi.org/10.1210/en.2010-1059

    Article  CAS  PubMed  Google Scholar 

  12. Li Q, Baines KJ, Gibson PG, Wood LG (2016) Changes in expression of genes regulating airway inflammation following a high-fat mixed meal in asthmatics. Nutrients. https://doi.org/10.3390/nu8010030

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sturchler E, Cox JA, Durussel I, Weibel M, Heizmann CW (2006) S100A16, a novel calcium-binding protein of the EF-hand superfamily. J Biol Chem 281(50):38905–38917. https://doi.org/10.1074/jbc.M605798200

    Article  CAS  PubMed  Google Scholar 

  14. Xu HF, Luo J, Zhao WS, Yang YC, Tian HB, Shi HB, Bionaz M (2016) Overexpression of SREBP1 (sterol regulatory element binding protein 1) promotes de novo fatty acid synthesis and triacylglycerol accumulation in goat mammary epithelial cells. J Dairy Sci 99(1):783–795. https://doi.org/10.3168/jds.2015-9736

    Article  CAS  PubMed  Google Scholar 

  15. Williams KJ, Argus JP, Zhu Y, Wilks MQ, Marbois BN, York AG, Kidani Y, Pourzia AL, Akhavan D, Lisiero DN, Komisopoulou E, Henkin AH, Soto H, Chamberlain BT, Vergnes L, Jung ME, Torres JZ, Liau LM, Christofk HR, Prins RM, Mischel PS, Reue K, Graeber TG, Bensinger SJ (2013) An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer Res 73(9):2850–2862. https://doi.org/10.1158/0008-5472.CAN-13-0382-T

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu C, Zhuo H, Ye MY, Huang GX, Fan M, Huang XZ (2020) LncRNA MALAT1 promoted high glucose-induced pyroptosis of renal tubular epithelial cell by sponging miR-30c targeting for NLRP3. Kaohsiung J Med Sci. https://doi.org/10.1002/kjm2.12226

    Article  PubMed  Google Scholar 

  17. Cao Z, Cooper ME (2011) Pathogenesis of diabetic nephropathy. J Diabetes Investig 2(4):243–247. https://doi.org/10.1111/j.2040-1124.2011.00131.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yacoub R, Campbell KN (2015) Inhibition of RAS in diabetic nephropathy. Int J Nephrol Renovasc Dis 8:29–40. https://doi.org/10.2147/IJNRD.S37893

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ferrao FM, Lara LS, Lowe J (2014) Renin-angiotensin system in the kidney: what is new? World J Nephrol 3(3):64–76. https://doi.org/10.5527/wjn.v3.i3.64

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mohamed RH, Abdel-Aziz HR, Abd El Motteleb DM, Abd El-Aziz TA (2013) Effect of RAS inhibition on TGF-beta, renal function and structure in experimentally induced diabetic hypertensive nephropathy rats. Biomed Pharmacother 67(3):209–214. https://doi.org/10.1016/j.biopha.2009.08.002

    Article  CAS  PubMed  Google Scholar 

  21. Lv N, Li C, Liu X, Qi C, Wang Z (2019) miR-34b Alleviates high glucose-induced inflammation and apoptosis in human HK-2 cells via IL-6R/JAK2/STAT3 signaling pathway. Med Sci Monit 25:8142–8151. https://doi.org/10.12659/MSM.917128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang J, Zhao X, Zhu H, Wang J, Ma J, Gu M (2019) Apigenin protects against renal tubular epithelial cell injury and oxidative stress by high glucose via regulation of NF-E2-related factor 2 (Nrf2) pathway. Med Sci Monit 25:5280–5288. https://doi.org/10.12659/MSM.915038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dominguez B, Pardo BG, Noia M, Millan A, Gomez-Tato A, Martinez P, Leiro J, Lamas J (2013) Microarray analysis of the inflammatory and immune responses in head kidney turbot leucocytes treated with resveratrol. Int Immunopharmacol 15(3):588–596. https://doi.org/10.1016/j.intimp.2013.01.024

    Article  CAS  PubMed  Google Scholar 

  24. Wang X, Sato R, Brown MS, Hua X, Goldstein JL (1994) SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77(1):53–62. https://doi.org/10.1016/0092-8674(94)90234-8

    Article  CAS  PubMed  Google Scholar 

  25. Xu M, Jiang F, Li B, Zhang Z (2019) 1Alpha, 25(OH)2 D3 alleviates high glucose-induced lipid accumulation in rat renal tubular epithelial cells by inhibiting SREBPs. J Cell Biochem 120(9):15211–15221. https://doi.org/10.1002/jcb.28786

    Article  CAS  PubMed  Google Scholar 

  26. Sun H, Yuan Y, Sun ZL (2013) Cholesterol contributes to diabetic nephropathy through SCAP-SREBP-2 pathway. Int J Endocrinol 2013:592576. https://doi.org/10.1155/2013/592576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang XX, Levi J, Luo Y, Myakala K, Herman-Edelstein M, Qiu L, Wang D, Peng Y, Grenz A, Lucia S, Dobrinskikh E, D’Agati VD, Koepsell H, Kopp JB, Rosenberg AZ, Levi M (2017) SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J Biol Chem 292(13):5335–5348. https://doi.org/10.1074/jbc.M117.779520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD (2012) The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab 15(2):240–246. https://doi.org/10.1016/j.cmet.2011.12.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jiang X, Yu J, Wang X, Ge J, Li N (2019) Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy. Diabetes Metab Syndr Obes 12:827–839. https://doi.org/10.2147/DMSO.S195456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, Zhangzhou Affiliated Hospital of Fujian Medical University, NO. 59 Shengli Road, Xiangcheng District, Zhangzhou, 363000, Fujian, China

    Lanlan Liu & Shan Lan

Authors
  1. Lanlan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shan Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lanlan Liu.

Ethics declarations

Conflict of interest

The authors declare that there is no potential interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, L., Lan, S. Interference of S100A16 suppresses lipid accumulation and inflammation in high glucose-induced HK-2 cells. Int Urol Nephrol 53, 1255–1263 (2021). https://doi.org/10.1007/s11255-020-02731-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-020-02731-4

Keywords

Search

Navigation