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Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis

  • Authors:
    • Xing Chen
    • Xiao‑Ming Hou
    • You‑Fei Fan
    • Yu‑Ting Jin
    • Yu‑Lin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2929-2936
    |
    Published online on: August 9, 2016
       https://doi.org/10.3892/mmr.2016.5614
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Abstract

The sonic hedgehog (SHH) morphogen regulates cell differentiation and controls a number of genes during renal morphogenesis. To date, the effects of SHH on fibroblast growth factors (Fgfs) in embryonic kidney development remain unclear. In the present study, explants of BALB/c mouse embryonic kidney tissues were used to investigate the role of exogenous SHH on Fgf8 and Fgf10 expression levels ex vivo. Ureteric bud branches and epithelial metanephric derivatives were used to determine the renal morphogenesis with Dolichos biflorus agglutinin or hematoxylin‑eosin staining. mRNA expression levels were determined using reverse transcription‑quantitative polymerase chain reaction, while the protein expression levels were examined using immunohistochemistry and western blot analysis. During the initial stages of metanephric development, low levels of SHH, Fgf8, and Fgf10 expression were observed, which were found to increase significantly during more advanced stages of metanephric development. In addition, exogenous SHH protein treatment increased the number of ureteric bud branches and enhanced the formation of nephrons. Exogenous SHH reduced the Fgf8 mRNA and protein expression levels, whereas cyclopamine (an SHH‑smoothened receptor inhibitor) interfered with SHH‑mediated downregulation of Fgf8 expression. By contrast, exogenous SHH protein was not found to modulate Fgf10 mRNA and protein expression levels. In conclusion, these results indicate that the modulatory effects of SHH on BALB/c mouse metanephric explant cultures may involve the regulation of Fgf8 expression but not Fgf10 expression, which provides evidence for the functional role of Fgf proteins in renal morphogenesis.
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1 

Gill PS and Rosenblum ND: Control of murine kidney development by sonic hedgehog and its GLI effectors. Cell cycle. 5:1426–1430. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Shah MM, Sampogna RV, Sakurai H, Bush KT and Nigam SK: Branching morphogenesis and kidney disease. Development. 131:1449–1462. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Reidy KJ and Rosenblum ND: Cell and molecular biology of kidney development. Semin Nephrol. 29:321–337. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Piscione TD and Rosenblum ND: The molecular control of renal branching morphogenesis: Current knowledge and emerging insights. Differentiation. 70:227–246. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Bai CB, Auerbach W, Lee JS, Stephen D and Joyner AL: Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 129:4753–4761. 2002.PubMed/NCBI

6 

Park HL, Bai C, Platt KA, Matise MP, Beeghly A, Hui CC, Nakashima M and Joyner AL: Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development. 127:1593–1605. 2000.PubMed/NCBI

7 

Ding H, Zhou D, Hao S, Zhou L, He W, Nie J, Hou FF and Liu Y: Sonic hedgehog signaling mediates epithelial-mesenchymal communication and promotes renal fibrosis. J Am Soc Nephrol. 23:801–813. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Lurie IW, Ilyina HG, Podleschuk LV, Gorelik LB and Zaletajev DV: Chromosome 7 abnormalities in parents of children with holoprosencephaly and hydronephrosis. Am J Med Genet. 35:286–288. 1990. View Article : Google Scholar : PubMed/NCBI

9 

Nowaczyk MJ, Huggins MJ, Tomkins DJ, Rossi E, Ramsay JA, Woulfe J, Scherer SW and Belloni E: Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency. Clin Genet. 57:388–393. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Kim PC, Mo R and Hui Cc C: Murine models of VACTERL syndrome: Role of sonic hedgehog signaling pathway. J Pediatr Surg. 36:381–384. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Yu J, Carroll TJ and McMahon AP: Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development. 129:5301–5312. 2002.PubMed/NCBI

12 

Grieshammer U, Cebrián C, Ilagan R, Meyers E, Herzlinger D and Martin GR: FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 132:3847–3857. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S and Itoh N: FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun. 277:643–649. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Qiao J, Uzzo R, Obara-Ishihara T, Degenstein L, Fuchs E and Herzlinger D: FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development. 126:547–554. 1999.PubMed/NCBI

15 

Barasch J, Qiao J, McWilliams G, Chen D, Oliver JA and Herzlinger D: Ureteric bud cells secrete multiple factors, including bFGF, which rescue renal progenitors from apoptosis. Am J Physiol. 273:F757–F767. 1997.PubMed/NCBI

16 

Poladia DP, Kish K, Kutay B, Hains D, Kegg H, Zhao H and Bates CM: Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 291:325–339. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Zhao H, Kegg H, Grady S, Truong HT, Robinson ML, Baum M and Bates CM: Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol. 276:403–415. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Perantoni AO, Timofeeva O, Naillat F, Richman C, Pajni-Underwood S, Wilson C, Vainio S, Dove LF and Lewandoski M: Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development. 132:3859–3871. 2005. View Article : Google Scholar : PubMed/NCBI

19 

White AC, Xu J, Yin Y, Smith C, Schmid G and Ornitz DM: FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains. Development. 133:1507–1517. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Zhang Z, Verheyden JM, Hassell JA and Sun X: FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Dev Cell. 16:607–613. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Mukhopadhyay A, Krishnaswami SR, Cowing-Zitron C, Hung NJ, Reilly-Rhoten H, Burns J and Yu BD: Negative regulation of Shh levels by Kras and Fgfr2 during hair follicle development. Devel Biol. 373:373–382. 2013. View Article : Google Scholar

22 

Haworth KE, Wilson JM, Grevellec A, Cobourne MT, Healy C, Helms JA, Sharpe PT and Tucker AS: Sonic hedgehog in the pharyngeal endoderm controls arch pattern via regulation of Fgf8 in head ectoderm. Dev Biol. 303:244–258. 2007. View Article : Google Scholar

23 

Gupta IR, Lapointe M and Yu OH: Morphogenesis during mouse embryonic kidney explant culture. Kidney Int. 63:365–376. 2003. View Article : Google Scholar

24 

Hoy WE, Douglas-Denton RN, Hughson MD, Cass A, Johnson K and Bertram JF: A stereological study of glomerular number and volume: Preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl. S31–S37. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Barak H and Boyle SC: Organ culture and immunostaining of mouse embryonic kidneys. Cold Spring Harb Protoc. 2011:pdb.prot55582011. View Article : Google Scholar : PubMed/NCBI

26 

Narlis M, Grote D, Gaitan Y, Boualia SK and Bouchard M: Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. J Am Soc Nephrol. 18:1121–1129. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Chai L, Yang J, Di C, Cui W, Kawakami K, Lai R and Ma Y: Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development. J Biol Chem. 281:18918–18926. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Murashima A, Akita H, Okazawa M, Kishigami S, Nakagata N, Nishinakamura R and Yamada G: Midline-derived Shh regulates mesonephric tubule formation through the paraxial mesoderm. Dev Biol. 386:216–226. 2014. View Article : Google Scholar :

29 

Pedersen A, Skjong C and Shawlot W: Lim 1 is required for nephric duct extension and ureteric bud morphogenesis. Dev Biol. 288:571–581. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Sun X, Meyers EN, Lewandoski M and Martin GR: Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev. 13:1834–1846. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Igarashi M, Finch PW and Aaronson SA: Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem. 273:13230–13235. 1998. View Article : Google Scholar : PubMed/NCBI

32 

Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N and Kato S: Fgf10 is essential for limb and lung formation. Nat Genet. 21:138–141. 1999. View Article : Google Scholar : PubMed/NCBI

33 

Michos O, Cebrian C, Hyink D, Grieshammer U, Williams L, D'Agati V, Licht JD, Martin GR and Costantini F: Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet. 6:e10008092010. View Article : Google Scholar : PubMed/NCBI

34 

Xu X, Weinstein M, Li C, Naski M, Cohen RI, Ornitz DM, Leder P and Deng C: Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development. 125:753–765. 1998.PubMed/NCBI

35 

Watanabe Y, Miyagawa-Tomita S, Vincent SD, Kelly RG, Moon AM and Buckingham ME: Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial pole of the heart and pharyngeal arch arteries. Circ Res. 106:495–503. 2010. View Article : Google Scholar :

36 

Urban AE, Zhou X, Ungos JM, Raible DW, Altmann CR and Vize PD: FGF is essential for both condensation and mesenchymal-epithelial transition stages of pronephric kidney tubule development. Dev Biol. 297:103–117. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Guo W, Yi X, Ren F, Liu L, Wu S and Yang J: Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury. Int J Clin Exp Pathol. 8:12464–12472. 2015.

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Copy and paste a formatted citation
Spandidos Publications style
Chen X, Hou XM, Fan YF, Jin YT and Wang YL: Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis. Mol Med Rep 14: 2929-2936, 2016.
APA
Chen, X., Hou, X., Fan, Y., Jin, Y., & Wang, Y. (2016). Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis. Molecular Medicine Reports, 14, 2929-2936. https://doi.org/10.3892/mmr.2016.5614
MLA
Chen, X., Hou, X., Fan, Y., Jin, Y., Wang, Y."Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis". Molecular Medicine Reports 14.4 (2016): 2929-2936.
Chicago
Chen, X., Hou, X., Fan, Y., Jin, Y., Wang, Y."Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis". Molecular Medicine Reports 14, no. 4 (2016): 2929-2936. https://doi.org/10.3892/mmr.2016.5614
Copy and paste a formatted citation
x
Spandidos Publications style
Chen X, Hou XM, Fan YF, Jin YT and Wang YL: Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis. Mol Med Rep 14: 2929-2936, 2016.
APA
Chen, X., Hou, X., Fan, Y., Jin, Y., & Wang, Y. (2016). Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis. Molecular Medicine Reports, 14, 2929-2936. https://doi.org/10.3892/mmr.2016.5614
MLA
Chen, X., Hou, X., Fan, Y., Jin, Y., Wang, Y."Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis". Molecular Medicine Reports 14.4 (2016): 2929-2936.
Chicago
Chen, X., Hou, X., Fan, Y., Jin, Y., Wang, Y."Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis". Molecular Medicine Reports 14, no. 4 (2016): 2929-2936. https://doi.org/10.3892/mmr.2016.5614
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