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International Journal of Colorectal Disease

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01-12-2011 | Original Article

Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing

Authors: Levilester Salcedo, Nikolai Sopko, Hai-Hong Jiang, Margot Damaser, Marc Penn, Massarat Zutshi

Published in: International Journal of Colorectal Disease | Issue 12/2011

Abstract

Purpose

Stromal derived factor-1 (SDF-1) and monocyte chemotactic protein-3 (MCP-3) are signals forcing the migration of bone marrow-derived stem cells to ischemic tissue. This study investigates SDF-1 and MCP-3 expression following direct injury to the anal sphincter and pudendal nerve and to determine if these same mechanisms have any role.

Methods

Chemokine expression was studied after anal sphincter injury in female rats after either a sphincterotomy (n = 15), pudendal nerve crush (PNC; n = 15), sham pudendal nerve crush (n = 15), or acted as unmanipulated controls (n = 5). Analysis was done at 1 h and 10 and 21 days after injury.

Results

After injury, SDF-1 expression increased 40.2 ± 6.42 (P = 0.01) at 1 h and 28.2 ± 2.37 (P = 0.01) at 10 days, respectively, compared to controls. Likewise, MCP-3 expression increased 40.8 ± 8.17 (P = 0.02) at the same intervals compared to controls. After PNC, SDF-1 expression increased 46.4 ± 6.01 (P = 0.02) and 50.6 ± 10.11 (P = 0.01), and MCP-3 expression increased 46.3 ± 7.76 (P = 0.03) and 190.8 ± 22.15 (P = 0.01), respectively, at the same time intervals compared to controls. However, when PNC was compared to sham injured, a significant increase was seen in SDF-1 and MCP-3 at 10 days. At 21 days, PNC compared to sham injured was significantly low in expression for both SDF-1 and MCP-3 (P < 0.05).

Conclusions

Direct anal sphincter injury results in higher levels of SDF-1 and MCP-3 expression soon after injury, whereas denervation via pudendal nerve crush results in greater SDF-1 and MCP-3 expression 10 days after injury. Chemokine overexpression suggests the potential for cell-based therapeutic strategies.

Thornton M, Lubowski D (2006) Obstetric-induced incontinence: a black hole of preventable morbidity. Aust N Z J Obstet Gynaecol 46:468–473PubMedCrossRef

Wang A, Guess M, Connell K et al (2006) Fecal incontinence: a review of prevalence and obstetric risk factors. Int Urogynecol J Pelvic Floor Dysfunct 17:253–260PubMedCrossRef

Fernando R, Sultan AH, Kettle C et al (2006) Methods of repair for obstetric anal sphincter injury. Cochrane Database of Syst Rev 3:CD002866

Malouf AJ, Chambers MG, Kamm MA (2001) Clinical and economic evaluation of surgical treatments for faecal incontinence. Br J Surg 88:1029–1036PubMedCrossRef

White FA, Bhangoo SK, Miller RJ (2005) Chemokines: integrators of pain and inflammation. Nat Rev Drug Discov 4:834–844PubMedCrossRef

Luster AD (1998) Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445PubMedCrossRef

Schenk S, Mal N, Finan A et al (2007) Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor. Stem Cells 25:245–251PubMedCrossRef

Zhang M, Mal N, Kiedrowski M et al (2007) SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. Faseb J 21:3197–3207PubMedCrossRef

Penn MS, Khalil MK (2008) Exploitation of stem cell homing for gene delivery. Expert Opin Biol Ther 8:17–30PubMedCrossRef

10.

Penn MS, Francis GS, Ellis SG et al (2002) Autologous cell transplantation for the treatment of damaged myocardium. Prog Cardiovasc Dis 45:21–32PubMedCrossRef

11.

Penn MS (2009) Importance of the SDF-1:CXCR4 axis in myocardial repair. Circ Res 104:1133–1135PubMedCrossRef

12.

Woo LL, Hijaz A, Kuang M et al (2007) Over expression of stem cell homing cytokines in urogenital organs following vaginal distention. J Urol 177:1568–1572PubMedCrossRef

13.

Zutshi M, Salcedo L, Hui P et al (2009) Rat anal sphincter physiology after pudendal nerve transection and sphincterotomy. Dis Colon Rectum 52:1321–1329PubMedCrossRef

14.

Damaser MS, Broxton-King C, Ferguson C et al (2003) Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat. J Urol 170:1027–1031PubMedCrossRef

15.

Yin JL, Shackel NA, Zekry A et al (2001) Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green I. Immunol Cell Biol 79:213–221PubMedCrossRef

16.

Dudding TC, Vaizey CJ, Kamm MA (2008) Obstetric anal sphincter injury—incidence, risk factors, and management. Ann Surg 247:224–237PubMedCrossRef

17.

Handa VL, Zyczynski HM, Burgio KL et al (2007) The impact of fecal and urinary incontinence on quality of life 6 months after childbirth. Am J Obstet Gynecol 197:636.e1–636.e6CrossRef

18.

Crowell MD, Schettler VA, Lacy BE et al (2007) Impact of anal incontinence on psychosocial function and health-related quality of life. Dig Dis Sci 52:1627–1631PubMedCrossRef

19.

Eogan M, O'Herlihy C (2006) Diagnosis and management of obstetric anal sphincter injury. Curr Opin Obstet Gynecol 18:141–146PubMedCrossRef

20.

Fitzgerald MP, Weber AM, Howden N et al (2007) Risk factors for anal sphincter tear during vaginal delivery. Obstet Gynecol 109:29–34PubMedCrossRef

21.

Lien KC, Morgan DM, Delancey JOL et al (2005) Pudendal nerve stretch during vaginal birth: a 3D computer simulation. Am J Obstet Gynecol 192:1669–1676PubMedCrossRef

22.

Safioleas M, Andromanakos N, Lygidakis N (2008) Anorectal incontinence: therapeutic strategy of a complex surgical problem. Hepatogastroenterology 55:1320–1326PubMed

23.

Schiedeck THK (2008) Diagnosis and therapy of stool incontinence. Chirurg 79:379–388PubMedCrossRef

24.

Halverson AL, Hull TL (2002) Long-term outcome of overlapping anal sphincter repair. Dis Colon Rectum 45:345–348PubMedCrossRef

25.

de Paula PR, Matos D, Franco M et al (2004) Why do anal wounds heal adequately? A study of the local immunoinflammatory defense mechanisms. Dis Colon Rectum 47:1861–1867PubMedCrossRef

26.

Rosenkilde MM, Schwartz TW (2004) The chemokine system—a major regulator of angiogenesis in health and disease. APMIS 112:481–495PubMedCrossRef

27.

Nath C, Gulati SC (1998) Role of cytokines in healing chronic skin wounds. Acta Haematol 99:175–179PubMedCrossRef

28.

Spadaro JA (1997) Mechanical and electrical interactions in bone remodeling. Bioelectromagnetics 18:193–202PubMedCrossRef

29.

Aloisi F, Columba-Cabezas S, Franciotta D et al (2008) Lymphoid chemokines in chronic neuroinflammation. J Neuroimmunol 198:106–112PubMedCrossRef

30.

Khatami M (2008) 'Yin and Yang' in inflammation: duality in innate immune cell function and tumorigenesis. Expert Opin Biol Ther 8:1461–1472PubMedCrossRef

31.

Liu C, Papewalis C, Domberg J et al (2008) Chemokines and autoimmune thyroid diseases. Horm Metab Res 40:361–368PubMedCrossRef

32.

Rovin BH (2008) The chemokine network in systemic lupus erythematous nephritis. Front Biosci 13:904–922PubMedCrossRef

33.

Shames BD, Zallen GS, McIntyre RC et al (2000) Chemokines as mediators of diseases related to surgical conditions. Shock 14:1–7PubMedCrossRef

34.

Miller RJ, Tran PB (2005) Chemokinetics. Neuron 47:621–623PubMedCrossRef

35.

Jiang HH, Pan HQ, Gustilo-Ashby MA et al (2009) Dual simulated childbirth injuries result in slowed recovery of pudendal nerve and urethral function. Neurourol Urodyn 28:229–235PubMedCrossRef

36.

Wai CY, Rahn DD, White AB et al (2008) Recovery of external anal sphincter contractile function after prolonged vaginal distention or sphincter transection in an animal model. Obstet Gynecol 111:1426–1434PubMedCrossRef

37.

Deister C, Schmidt CE (2006) Optimizing neurotrophic factor combinations for neurite outgrowth. J Neural Eng 3:172–179PubMedCrossRef

38.

English AW (2003) Cytokines, growth factors and sprouting at the neuromuscular junction. J Neurocytol 32:943–960PubMedCrossRef

39.

Chang CH, Rossi EA, Goldenberg DM (2007) The dock and lock method: a novel platform technology for building multivalent, multifunctional structures of defined composition with retained bioactivity. Clin Cancer Res 13:5586S–5591SPubMedCrossRef

Title: Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing
Authors: Levilester Salcedo
Nikolai Sopko
Hai-Hong Jiang
Margot Damaser
Marc Penn
Massarat Zutshi
Publication date: 01-12-2011
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 12/2011
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-011-1269-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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