EXPRESSION OF Sonic Hedgehog SIGNALING PATHWAY AFTER SPINAL CORD INJURY IN ADULT RATS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CUIZhaohui , TENGYuanjun , JIANGJin , XIAYayi , WANGJing , ANLiping , MAJinglin ,  WANLin

Orthopaedic Key Laboratory of Gansu Province, the Second Hospital of Lanzhou University, Lanzhou Gansu, 730000, P. R. China;

Corresponding author：

WANLin, Email: plkoiujght@163.com

Keywords：

Spinal cord injury; Sonic Hedgehog signaling pathway; Glioma-associated oncogene homolog-1; Nerve regeneration

DOI：

10.7507/1002-1892.20150125

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression pattern and significance of Sonic Hedgehog (Shh) signaling pathway by observing whether the Shh signaling pathway components express in the adult rat after spinal cord injury (SCI). Methods Sixty-four healthy male Sprague-Dawley rats were randomly divided into normal group (group A, 8 rats), sham group (group B, 8 rats), and SCI group (group C, 48 rats). In group A, the rats served as controls without any treatment; a decompressive laminectomy was performed on T_7-9 levels without SCI in group B; and modified Allen's method was used to make SCI model in group C. Basso Beattie Bresnahan (BBB) scale was used to assess the hind limb motor function at 12 hours, 1 day, 3 days, 7 days, 14 days, and 21 days after SCI; the immunofluorescence staining, real-time PCR, and Western blot were performed to detect the mRNA and protein expression levels of Shh and Glioma-associated oncogene homolog-1 (Gli-1) in SCI zone. Results The BBB score slowly increased with time in group C, but the scores at each time point in group C were significantly lower than those in group A and group B (P<0.05). The results of immunofluorescence staining showed that Shh and Gli-1 rapidly increased after SCI in astrocytes. Real-time PCR and Western blot showed that the relative expression levels of Shh and Gli-1 mRNA and protein were gradually increased in group C and reached a maximum at 7 days. In addition, the relative expression levels of Shh and Gli-1 mRNA and protein in group C were significantly higher than those in group A and group B (P<0.05). On the other hand, compared with group A, the expression of Gli-1 protein was reduced in the cytoplasm but increased in nucleus in group C. Conclusion Astrocytes synthesize and secrete Shh and Gli-1 signaling molecules after SCI, both Shh and Gli-1 significantly up-regulate and exhibit dynamic changes, which suggests Shh signaling pathway may be involved in nerve cell regeneration after SCI.

Citation： CUIZhaohui, TENGYuanjun, JIANGJin, XIAYayi, WANGJing, ANLiping, MAJinglin, WANLin. EXPRESSION OF Sonic Hedgehog SIGNALING PATHWAY AFTER SPINAL CORD INJURY IN ADULT RATS. Chinese Journal of Reparative and Reconstructive Surgery, 2015, 29(5): 576-581. doi: 10.7507/1002-1892.20150125 Copy

1.	Schwab ME. Repairing the injured spinal cord. Science, 2002, 295(5557):1029-1031.
2.	Fuccillo M, Joyner AL, Fishell G. Morphogen to mitogen:the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci, 2006, 7(10):772-783.
3.	Watkins DN, Berman DM, Burkgolder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature, 2003, 422(6929):313-317.
4.	Thayer SP, di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003, 425(6960):851-856.
5.	Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature, 2004, 431(7009):707-712.
6.	Ohta M, Tateishi K, Kanai F, et al. p53-Independent negative regulation of p21/cyclin-dependent kinase-interacting protein 1 by the sonic hedgehog-glioma-associated oncogene 1 pathway in gastric carcinoma cells. Cancer Res, 65(23):10822-10829.
7.	Kubo M, Nakamura M, Tasaki A, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res, 64(17):6071-6074.
8.	Atkinson PJ, Dellovade T, Albers D, et al. Sonic Hedgehog signaling in astrocytes is dependent on p38 mitogen-activated protein kinase and G-protein receptor kinase 2. J Neurochem. 2009, 108(6):1539-1549.
9.	Dai RL, Zhu SY, Xia YP, et al. Sonic hedgehog protects cortical neurons against oxidative stress. Neurochem Res, 2011, 36(1):67-75.
10.	庞清江, 罗永湘. 实验性脊髓损伤模型的建立. 中国修复重建外科杂志, 1995, 9(2):120-122.
11.	Engesser-Cesar C, Anderson AJ, Basso DM, et al. Voluntary wheel running improves recovery from a moderate spinal cord injury. Neurotrauma, 2005, 22(1):157-171.
12.	Cajal SRY. Cajal's degeneration and regeneration of the nervous system. London:Oxford University Press, 1928:105.
13.	Johansson CB, Svensson M, Wallstedt L, et al. Neural stem cells in the adult human brain. Exp Cell Res, 1999, 253(2):733-736.
14.	Shin SH, Kogerman P, Lindström E, et al. GLI3 mutations in human disorders mimic Drosophila cubitus interruptus protein functions and localization. Proc Natl Acad Sci U S A, 1999, 96(6):2880-2884.
15.	Lipinski RJ, Gipp JJ, Zhang J, et al. Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling. Exp Cell Res, 2006, 312(11):1925-1938.
16.	Sims JR, Lee SW, Topalkara K, et al. Sonic hedgehog regulates ischemia/hypoxia-induced neural progenitor proliferation. Stroke, 2009, 40(11):3618-3626.
17.	Mao L, Xia YP, Zhou YN, et al. Activation of sonic hedgehog signaling pathway in olfactory neuroblastoma. Oncology, 2009, 77(3-4):231-243.
18.	崔兆辉, 董海涛, 姜金, 等. 成年大鼠脊髓损伤后内源性神经前体细胞的增殖与分化规律的研究. 世界科技研究与发展杂志, 2014, 36(5):521-525.
19.	Buttitta L, Mo R, Hui CC, et al. Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction. Development, 2003, 130(25):6233-6243.
20.	Eichberger T, Sander V, Schnidar H, et al. Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes. Genomics, 2006, 87(5):616-632.
21.	Lai K, Kaspar BK, Gage FH, et al. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci, 2003, 6(1):21-27.
22.	Morita K, Lo Celso C, Spencer-Dene B, et al. HAN11 binds mDia1 and controls GLI1 transcriptional activity. J Dermatol Sci, 2006, 44(1):11-20.
23.	Nolan-Stevaux O, Lau J, Truitt ML, et al. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev, 2009, 23(1):24-36.

1. Schwab ME. Repairing the injured spinal cord. Science, 2002, 295(5557):1029-1031.
2. Fuccillo M, Joyner AL, Fishell G. Morphogen to mitogen:the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci, 2006, 7(10):772-783.
3. Watkins DN, Berman DM, Burkgolder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature, 2003, 422(6929):313-317.
4. Thayer SP, di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003, 425(6960):851-856.
5. Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature, 2004, 431(7009):707-712.
6. Ohta M, Tateishi K, Kanai F, et al. p53-Independent negative regulation of p21/cyclin-dependent kinase-interacting protein 1 by the sonic hedgehog-glioma-associated oncogene 1 pathway in gastric carcinoma cells. Cancer Res, 65(23):10822-10829.
7. Kubo M, Nakamura M, Tasaki A, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res, 64(17):6071-6074.
8. Atkinson PJ, Dellovade T, Albers D, et al. Sonic Hedgehog signaling in astrocytes is dependent on p38 mitogen-activated protein kinase and G-protein receptor kinase 2. J Neurochem. 2009, 108(6):1539-1549.
9. Dai RL, Zhu SY, Xia YP, et al. Sonic hedgehog protects cortical neurons against oxidative stress. Neurochem Res, 2011, 36(1):67-75.
10. 庞清江, 罗永湘. 实验性脊髓损伤模型的建立. 中国修复重建外科杂志, 1995, 9(2):120-122.
11. Engesser-Cesar C, Anderson AJ, Basso DM, et al. Voluntary wheel running improves recovery from a moderate spinal cord injury. Neurotrauma, 2005, 22(1):157-171.
12. Cajal SRY. Cajal's degeneration and regeneration of the nervous system. London:Oxford University Press, 1928:105.
13. Johansson CB, Svensson M, Wallstedt L, et al. Neural stem cells in the adult human brain. Exp Cell Res, 1999, 253(2):733-736.
14. Shin SH, Kogerman P, Lindström E, et al. GLI3 mutations in human disorders mimic Drosophila cubitus interruptus protein functions and localization. Proc Natl Acad Sci U S A, 1999, 96(6):2880-2884.
15. Lipinski RJ, Gipp JJ, Zhang J, et al. Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling. Exp Cell Res, 2006, 312(11):1925-1938.
16. Sims JR, Lee SW, Topalkara K, et al. Sonic hedgehog regulates ischemia/hypoxia-induced neural progenitor proliferation. Stroke, 2009, 40(11):3618-3626.
17. Mao L, Xia YP, Zhou YN, et al. Activation of sonic hedgehog signaling pathway in olfactory neuroblastoma. Oncology, 2009, 77(3-4):231-243.
18. 崔兆辉, 董海涛, 姜金, 等. 成年大鼠脊髓损伤后内源性神经前体细胞的增殖与分化规律的研究. 世界科技研究与发展杂志, 2014, 36(5):521-525.
19. Buttitta L, Mo R, Hui CC, et al. Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction. Development, 2003, 130(25):6233-6243.
20. Eichberger T, Sander V, Schnidar H, et al. Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes. Genomics, 2006, 87(5):616-632.
21. Lai K, Kaspar BK, Gage FH, et al. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci, 2003, 6(1):21-27.
22. Morita K, Lo Celso C, Spencer-Dene B, et al. HAN11 binds mDia1 and controls GLI1 transcriptional activity. J Dermatol Sci, 2006, 44(1):11-20.
23. Nolan-Stevaux O, Lau J, Truitt ML, et al. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev, 2009, 23(1):24-36.

Previous Article
EXPERIENCE IN MANAGEMENT OF OCCULT CEREBROSPINAL FLUID LEAKAGE IN POSTERIOR THORACOLUMBAR SURGERY
Next Article
EXTENDED NASOLABIAL FLAPS IN MANAGEMENT OF ANTERIOR BUCCAL MUCOSAL DEFECTS

Chinese Journal of Reparative and Reconstructive Surgery

EXPRESSION OF Sonic Hedgehog SIGNALING PATHWAY AFTER SPINAL CORD INJURY IN ADULT RATS

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content