Upregulation of TRPM7 augments cell proliferation and interleukin-8 release in airway smooth muscle cells of rats exposed to cigarette smoke

Lin,Xiaoling; Yang,Cheng; Huang,Linjie; Chen,Ming; Shi,Jianting; Ouyang,Lihua; Tang,Tiantian; Zhang,Wei; Li,Yiqun; Liang,Ruiyun; Jiang,Shanping

doi:10.3892/mmr.2016.5161

Upregulation of TRPM7 augments cell proliferation and interleukin-8 release in airway smooth muscle cells of rats exposed to cigarette smoke

Authors:
- Xiaoling Lin
- Cheng Yang
- Linjie Huang
- Ming Chen
- Jianting Shi
- Lihua Ouyang
- Tiantian Tang
- Wei Zhang
- Yiqun Li
- Ruiyun Liang
- Shanping Jiang
View Affiliations

Affiliations: Department of Respiratory Medicine, Sun Yat‑Sen Memorial Hospital, Institute of Respiratory Disease, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R, China, Department of Respiratory Medicine, Meizhou People's Hospital, Meizhou Affiliated Hospital of Sun Yat‑Sen University, Meizhou, Guangdong 514031, P.R. China
Published online on: April 22, 2016 https://doi.org/10.3892/mmr.2016.5161
Pages: 4995-5004
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Proliferation and synthetic function (i.e. the capacity to release numerous chemokines and cytokines) of airway smooth muscle cells (ASMCs) are important in airway remodeling induced by cigarette smoke exposure. However, the molecular mechanism has not been clarified. Transient receptor potential cation channel subfamily M member 7 (TRPM7) is expressed ubiquitously and is crucial for the cellular physiological function of many cell types. The present study aimed to detect the expression of TRPM7 in ASMCs from smoke‑exposed rats and determine the importance of TRPM7 in proliferation and interleukin‑8 (IL‑8) release. ASMCs were isolated and cultured from smoke‑exposed rats. Expression levels of TRPM7 were determined by reverse transcription‑polymerase chain reaction, western blot analysis and immunofluorescence. TRPM7 was silenced with TRPM7‑short hairpin RNA lentivirus vector. DNA synthesis, cell number and IL‑8 release of ASMCs induced by cigarette smoke extract (CSE) and tumor necrosis factor‑α (TNF‑α) were assessed using [3H]-thymidine incorporation assay, hemocytometer and enzyme‑linked immunosorbent assay, respectively. It was determined that mRNA and protein expression levels of TRPM7 were increased in ASMCs from smoke‑exposed rats. Stimulation with CSE or TNF‑α elevated DNA synthesis, cell number and IL‑8 release were more marked in ASMCs from smoke‑exposed rats. Silencing of TRPM7 reduced DNA synthesis, cell number and IL‑8 release induced by CSE or TNF‑α in ASMCs from smoke-exposed rats. In conclusion, expression of TRPM7 increased significantly in ASMCs from smoke‑exposed rats and the upregulation of TRPM7 led to augmented cell proliferation and IL-8 release in ASMCs from rats exposed to cigarette smoke.

View Figures

View References

1	Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al: Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: gold executive summary. Am J Respir Crit Care Med. 187:347–365. 2013. View Article : Google Scholar
2	Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, Maestrelli P, Ciaccia A and Fabbri LM: CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 157:822–826. 1998. View Article : Google Scholar : PubMed/NCBI
3	Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO and Paré PD: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 350:2645–2653. 2004. View Article : Google Scholar : PubMed/NCBI
4	Chung KF: The role of airway smooth muscle in the pathogenesis of airway wall remodeling in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2:347–354; discussion 371–372. 2005. View Article : Google Scholar : PubMed/NCBI
5	Stamatiou R, Paraskeva E, Gourgoulianis K, Molyvdas PA and Hatziefthimiou A: Cytokines and growth factors promote airway smooth muscle cell proliferation. ISRN Inflamm. 2012:7314722012. View Article : Google Scholar : PubMed/NCBI
6	Pera T, Gosens R, Lesterhuis AH, Sami R, van der Toorn M, Zaagsma J and Meurs H: Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype. Respir Res. 11:482010. View Article : Google Scholar : PubMed/NCBI
7	Howarth PH, Knox AJ, Amrani Y, Tliba O, Panettieri RA Jr and Johnson M: Synthetic responses in airway smooth muscle. J Allergy Clin Immunol. 114(Suppl 2): S32–S50. 2004. View Article : Google Scholar : PubMed/NCBI
8	Manetsch M, Seidel P, Heintz U, Che W, Hughes JM, Ge Q, Sukkar MB and Ammit AJ: TLR2 ligand engagement upregulates airway smooth muscle TNFα-induced cytokine production. Am J Physiol Lung Cell Mol Physiol. 302:L838–L845. 2012. View Article : Google Scholar : PubMed/NCBI
9	Baarsma HA, Meurs H, Halayko AJ, Menzen MH, Schmidt M, Kerstjens HA and Gosens R: Glycogen synthase kinase-3 regulates cigarette smoke extract- and IL-1β-induced cytokine secretion by airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 300:L910–L919. 2011. View Article : Google Scholar : PubMed/NCBI
10	Gosens R, Rieks D, Meurs H, Ninaber DK, Rabe KF, Nanninga J, Kolahian S, Halayko AJ, Hiemstra PS and Zuyderduyn S: Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells. Eur Respir J. 34:1436–1443. 2009. View Article : Google Scholar : PubMed/NCBI
11	Clapham DE: TRP channels as cellular sensors. Nature. 426:517–524. 2003. View Article : Google Scholar : PubMed/NCBI
12	Schmitz C, Perraud AL, Johnson CO, Inabe K, Smith MK, Penner R, Kurosaki T, Fleig A and Scharenberg AM: Regulation of vertebrate cellular Mg²⁺ homeostasis by TRPM7. Cell. 114:191–200. 2003. View Article : Google Scholar : PubMed/NCBI
13	Runnels LW, Yue L and Clapham DE: TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science. 291:1043–1047. 2001. View Article : Google Scholar : PubMed/NCBI
14	Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE and McNulty S: Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res. 26:159–178. 2006. View Article : Google Scholar : PubMed/NCBI
15	Kunert-Keil C, Bisping F, Krüger J and Brinkmeier H: Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics. 7:1592006. View Article : Google Scholar : PubMed/NCBI
16	Visser D, Middelbeek J, van Leeuwen FN and Jalink K: Function and regulation of the channel-kinase TRPM7 in health and disease. Eur J Cell Biol. 93:455–465. 2014. View Article : Google Scholar : PubMed/NCBI
17	Huang L, Ng NM, Chen M, Lin X, Tang T, Cheng H, Yang C and Jiang S: Inhibition of TRPM7 channels reduces degranulation and release of cytokines in rat bone marrow-derived mast cells. Int J Mol Sci. 15:11817–11831. 2014. View Article : Google Scholar : PubMed/NCBI
18	Chen M, Shi JT, Lv ZQ, Huang LJ, Lin XL, Zhang W, Liang RY, Li YQ and Jiang SP: Triptolide inhibits TGF-β1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-κB but not ERK1/2. Immunology. Sep 29–2014.Epub ahead of print. View Article : Google Scholar
19	Chen M, Lv Z, Huang L, Zhang W, Lin X, Shi J, Zhang W, Liang R and Jiang S: Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling. Exp Cell Res. 331:362–368. 2015. View Article : Google Scholar
20	Sahni J, Tamura R, Sweet IR and Scharenberg AM: TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes. Cell Cycle. 9:3565–3574. 2010. View Article : Google Scholar : PubMed/NCBI
21	Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, MacDonald JF and Tymianski M: A key role for TRPM7 channels in anoxic neuronal death. Cell. 115:863–877. 2003. View Article : Google Scholar : PubMed/NCBI
22	Touyz RM: Transient receptor potential melastatin 6 and 7 channels, magnesium transport and vascular biology: Implications in hypertension. Am J Physiol Heart Circ Physiol. 294:H1103–H1118. 2008. View Article : Google Scholar : PubMed/NCBI
23	Zeng Z, Inoue K, Sun H, Leng T, Feng X, Zhu L and Xiong ZG: TRPM7 regulates vascular endothelial cell adhesion and tube formation. Am J Physiol Cell Physiol. 308:C308–C318. 2015. View Article : Google Scholar :
24	Wykes RC, Lee M, Duffy SM, Yang W, Seward EP and Bradding P: Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival. J Immunol. 179:4045–4052. 2007. View Article : Google Scholar : PubMed/NCBI
25	Yu M, Huang C, Huang Y, Wu X, Li X and Li J: Inhibition of TRPM7 channels prevents proliferation and differentiation of human lung fibroblasts. Inflamm Res. 62:961–970. 2013. View Article : Google Scholar : PubMed/NCBI
26	Meng Z, Cao R, Wang Y, Cao H, Liu T, Yang Z and Wang X: Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation. World J Urol. 32:1303–1311. 2014. View Article : Google Scholar
27	Che H, Yue J, Tse HF and Li GR: Functional TRPV and TRPM channels in human preadipocytes. Pflugers Arch. 466:947–959. 2014. View Article : Google Scholar
28	Ng NM, Jiang SP and Lv ZQ: Retrovirus-mediated siRNA targeting TRPM7 gene induces apoptosis in RBL-2H3 cells. Eur Rev Med Pharmacol Sci. 16:1172–1178. 2012.PubMed/NCBI
29	Jiang J, Li MH, Inoue K, Chu XP, Seeds J and Xiong ZG: Transient receptor potential melastatin 7-like current in human head and neck carcinoma cells: Role in cell proliferation. Cancer Res. 67:10929–10938. 2007. View Article : Google Scholar : PubMed/NCBI
30	Guilbert A, Gautier M, Dhennin-Duthille I, Haren N, Sevestre H and Ouadid-Ahidouch H: Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol. 297:C493–C502. 2009. View Article : Google Scholar : PubMed/NCBI
31	Mishra R, Rao V, Ta R, Shobeiri N and Hill CE: Mg2+- and MgATP-inhibited and Ca2+/calmodulin-sensitive TRPM7-like current in hepatoma and hepatocytes. Am J Physiol Gastrointest Liver Physiol. 297:G687–G694. 2009. View Article : Google Scholar : PubMed/NCBI
32	Kim BJ, Kim SY, Lee S, Jeon JH, Matsui H, Kwon YK, Kim SJ and So I: The role of transient receptor potential channel blockers in human gastric cancer cell viability. Can J Physiol Pharmacol. 90:175–186. 2012. View Article : Google Scholar : PubMed/NCBI
33	Sun Y, Selvaraj S, Varma A, Derry S, Sahmoun AE and Singh BB: Increase in serum Ca2+/Mg2+ ratio promotes proliferation of prostate cancer cells by activating TRPM7 channels. J Biol Chem. 288:255–263. 2013. View Article : Google Scholar :
34	Tanni SE, Pelegrino NR, Angeleli AY, Correa C and Godoy I: Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients. J Inflamm (Lond). 7:292010. View Article : Google Scholar
35	Chiang CH, Chuang CH and Liu SL: Transforming growth factor-β1 and tumor necrosis factor-α are associated with clinical severity and airflow limitation of COPD in an additive manner. Lung. 192:95–102. 2014. View Article : Google Scholar
36	Churg A, Dai J, Tai H, Xie C and Wright JL: Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am J Respir Crit Care Med. 166:849–854. 2002. View Article : Google Scholar : PubMed/NCBI
37	Churg A, Wang RD, Tai H, Wang X, Xie C and Wright JL: Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse. Am J Respir Crit Care Med. 170:492–498. 2004. View Article : Google Scholar : PubMed/NCBI
38	McKay S, Hirst SJ, Haas MB, de Jongste JC, Hoogsteden HC, Saxena PR and Sharma HS: Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells. Am J Respir Cell Mol Biol. 23:103–111. 2000. View Article : Google Scholar : PubMed/NCBI
39	Tliba O, Tliba S, Da Huang C, Hoffman RK, DeLong P, Panettieri RA Jr and Amrani Y: Tumor necrosis factor alpha modulates airway smooth muscle function via the autocrine action of interferon beta. J Biol Chem. 278:50615–50623. 2003. View Article : Google Scholar : PubMed/NCBI
40	Yee NS, Kazi AA and Yee RK: Cellular and developmental biology of TRPM7 channel-kinase: Implicated roles in cancer. Cells. 3:751–77. 2014. View Article : Google Scholar : PubMed/NCBI