高糖环境下抑瘤素对人皮肤成纤维细胞增殖和细胞外基质分泌的影响

刘露露; 符学铭; 薛碧宇; 薛斌

doi:10.16016/j.1000-5404.202011253

您当前的位置：

首页 >

文章列表页 >

高糖环境下抑瘤素对人皮肤成纤维细胞增殖和细胞外基质分泌的影响

基础医学 | 更新时间：2026-01-09

- 高糖环境下抑瘤素对人皮肤成纤维细胞增殖和细胞外基质分泌的影响
- Effect of oncostatin M on proliferation and secretion of extracellular matrix in human dermal fibroblasts in high glucose condition
- 第三军医大学学报 2021年43卷第10期页码：955-963
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202011253
  中图分类号：
- 收稿：2020-11-27，
  
  纸质出版：2021-05-30
- 稿件说明：
移动端阅览
刘露露, 符学铭, 薛碧宇, 等. 高糖环境下抑瘤素对人皮肤成纤维细胞增殖和细胞外基质分泌的影响[J]. 第三军医大学学报, 2021,43(10):955-963.

Lulu LIU, Xueming FU, Biyu XUE, et al. Effect of oncostatin M on proliferation and secretion of extracellular matrix in human dermal fibroblasts in high glucose condition[J]. Journal of Third Military Medical University, 2021, 43(10): 955-963.
刘露露, 符学铭, 薛碧宇, 等. 高糖环境下抑瘤素对人皮肤成纤维细胞增殖和细胞外基质分泌的影响[J]. 第三军医大学学报, 2021,43(10):955-963. DOI： 10.16016/j.1000-5404.202011253.

Lulu LIU, Xueming FU, Biyu XUE, et al. Effect of oncostatin M on proliferation and secretion of extracellular matrix in human dermal fibroblasts in high glucose condition[J]. Journal of Third Military Medical University, 2021, 43(10): 955-963. DOI： 10.16016/j.1000-5404.202011253.

摘要

Abstract

Objective

To investigate the effects of oncostatin M (OSM) on the proliferation and extracellular matrix secretion of human dermal fibroblasts (HDFs) in high glucose environment and its possible mechanism.

Methods

① Establishment of hyperglycemia model: HDFs were treated with 5

20 and 25 mmol/L glucose

respectively. MTT assay was used to detect the proliferation activity of cells cultured in high glucose for 24

36 or 48 h. Western blotting was used to detect the protein levels of ERK

p-ERK and CyclinD1 in the HDFs treated with 5 or 20 mmol/L glucose for 24

36 and 48 h. ② Optimal concentration of OSM on hyperglycemia model: the cells were treated with 20 mmol/L glucose (control group)

and 20 mmol/L glucose+25

100

200 ng/mL OSM

respectively. MTT assay was used to detect the proliferation of above cells cultured for 24

36 and 48 h. The protein expression of CollagenⅠ

CollagenⅢ and fibronectin was detected by Western blotting. ③ Mechanism of OSM on hyperglycemia model: the cells were divided into control group

high glucose group

high glucose+OSM group

and high glucose+OSM+ inhibitor PD98059 group. Cell cycle was determined by flow cytometry. The protein levels of ERK

p-ERK

CyclinD1

CollagenⅠ

CollagenⅢ

fibronectin and other related factors were detected by Western blotting. q-PCR was used to measure the levels of ERK1/2

CyclinD1

CollagenⅠ

CollagenⅢ and fibronectin in each group.

Results

Treatment of 20 mmol/L glucose resulted in significantly decreased proliferation activity (

0.001)

increased proportion of G

cells (

0.01) and decreased proportion of S-phase cells (

0.01)

and reduced expression of ERK

p-ERK

CyclinD1

CollagenⅠ

CollagenⅢ and fibronectin (

0.01

0.05) when compared with the control cells. While treatment of 100 ng/mL OSM for 48 h enhanced the proliferation activity (

0.001)

decreased the proportion of G

cells (

0.05) but elevated the proportion of S-phase cells (

0.05)

and raised protein levels of ERK

p-ERK

CyclinD1

CollagenⅠ

CollagenⅢ and fibronectin cells (all

0.01). q-PCR indicated similar results as Western blotting

and statistical differences were seen in the results of mRNA levels (all

0.05). When ERK pathway specific small molecule inhibitor PD98059 blocked ERK signaling pathway

the above effects were significantly reduced (

0.05).

Conclusion

OSM may reverse the inhibitory effect of high glucose on the proliferation and extracellular matrix secretion through ERK signaling pathway in HDFs.

关键词

Keywords

references

朱万博糖尿病患者创面难愈机制及治疗研究进展中国糖尿病杂志 2016 24 12 1135 1139 10.3969/j.issn.1006-6187.2016.12.18.ZHUWB 朱万博. 糖尿病患者创面难愈机制及治疗研究进展[J]. 中国糖尿病杂志, 2016, 24(12): 1135-1139. DOI: 10.3969/j.issn. 1006-6187.2016.12.18.

ZHU W B Research progress of the mechanism and treatment of diabetic non-healing wounds Chin J Diabetes 2016 24 12 1135 1139 10.3969/j.issn.1006-6187.2016.12.18 ZHU W B. Research progress of the mechanism and treatment of diabetic non-healing wounds[J]. Chin J Diabetes, 2016, 24(12): 1135-1139. DOI: 10.3969/j.issn.1006-6187.2016.12.18.

PATEL S SRIVASTAVA S SINGH M R Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing Biomed Pharmacother 2019 112 108615 10.1016/j.biopha.2019.108615 PATEL S, SRIVASTAVA S, SINGH M R, et al . Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing[J ] . Biomed Pharmacother, 2019, 112: 108615. DOI: 10.1016/j.biopha.2019.108615.

SHEDOEVA A LEAVESLEY D UPTON Z Wound healing and the use of medicinal plants Evid-Based Compl Alt 2019 2019 2684108 10.1155/2019/2684108 SHEDOEVA A, LEAVESLEY D, UPTON Z, et al . Wound healing and the use of medicinal plants[J ] . Evid-Based Compl Alt, 2019, 2019: 2684108. DOI: 10.1155/2019/2684108.

RODRIGUES M KOSARIC N BONHAM C A Wound healing: a cellular perspective Physiol Rev 2019 99 1 665 706 10.1152/physrev.00067.2017 RODRIGUES M, KOSARIC N, BONHAM C A, et al . Wound healing: a cellular perspective [J ] . Physiol Rev, 2019, 99(1): 665-706. DOI: 10.1152/physrev.00067.2017.

HAN G CEILLEY R Chronic wound healing: a review of current management and treatments Adv Ther 2017 34 3 599 610 10.1007/s12325-017-0478-y HAN G, CEILLEY R. Chronic wound healing: a review of current management and treatments[J]. Adv Ther, 2017, 34(3): 599-610. DOI: 10.1007/s12325-017-0478-y.

HEATHER E D P DESHKA S F MICHAEL T L Fibroblasts and wound healing: An update Regen Med 2018 13 5 491 495 10.2217/rme-2018-0073 HEATHER E D P, DESHKA S F, MICHAEL T L. Fibroblasts and wound healing: An update[J]. Regen Med, 2018, 13(5): 491-495. DOI: 10.2217/rme-2018-0073.

LEFRANCOIS T MEHTA K SULLIVAN V Evidence based review of literature on detriments to healing of diabetic foot ulcers Foot Ankle Surg 2017 23 4 215 224 10.1016/j.fas.2016.04.002 LEFRANCOIS T, MEHTA K, SULLIVAN V, et al . Evidence based review of literature on detriments to healing of diabetic foot ulcers[J ] . Foot Ankle Surg, 2017, 23(4): 215-224. DOI: 10.1016/j.fas.2016.04.002.

SALAZAR J J ENNIS W J KOH T J Diabetes medications: Impact oninflammation and wound healing J Diabetes Complicat 2016 30 4 746 752 10.1016/j.jdiacomp.2015.12.017 SALAZAR J J, ENNIS W J, KOH T J. Diabetes medications: Impact oninflammation and wound healing[J]. J Diabetes Complicat, 2016, 30(4): 746-752. DOI: 10.1016/j.jdiacomp.2015.12.017.

王晓雨张玉杰曲春安成纤维细胞在糖尿病患者创伤愈合中作用的研究进展中国细胞生物学学报 2019 41 4 710 714 10.11844/cjcb.2019.04.0021 王晓雨, 张玉杰, 曲春安, 等. 成纤维细胞在糖尿病患者创伤愈合中作用的研究进展[J]. 中国细胞生物学学报, 2019, 41(4): 710-714. DOI: 10.11844/cjcb.2019.04.0021.

WANG X Y ZHANG Y J QU C A Research advances of fibroblast in diabetic wound healing Chin J Cell Biol 2019 41 4 710 714 10.11844/cjcb.2019.04.0021 WANG X Y, ZHANG Y J, QU C A, et al . Research advances of fibroblast in diabetic wound healing[J ] . Chin J Cell Biol, 2019, 41(4): 710-714. DOI: 10.11844/cjcb.2019.04.0021.

HERMANNS H M Oncostatin M and interleukin-31: cytokines, receptors, signal transduction and physiology Cytokine Growth Factor Rev 2015 26 5 545 558 10.1016/j.cytogfr.2015.07.006 HERMANNS H M. Oncostatin M and interleukin-31: cytokines, receptors, signal transduction and physiology[J]. Cytokine Growth Factor Rev, 2015, 26(5): 545-558. DOI: 10.1016/j.cytogfr.2015.07.006.

黄旭陈韵岱曹丰抑瘤素M的研究进展中华老年多器官疾病杂志 2016 15 12 940 943 10.11915/j.issn.1671-5403.2016.12.224 黄旭, 陈韵岱, 曹丰. 抑瘤素M的研究进展[J]. 中华老年多器官疾病杂志, 2016, 15(12): 940-943. DOI: 10.11915/j.issn.1671-5403.2016.12.224.

HUANG X CHEN Y D CAO F Research progress of oncostatin M Chin J Mult Organ Dis Elder 2016 15 12 940 943 10.11915/j.issn.1671-5403.2016.12.224 HUANG X, CHEN Y D, CAO F. Research progress of oncostatin M[J]. Chin J Mult Organ Dis Elder, 2016, 15(12): 940-943. DOI: 10.11915/j.issn.1671-5403.2016.12.224.

王兆鹏车妍袁园抑瘤素M在心脏疾病中的研究进展中华老年心脑血管病杂志 2019 21 5 548 550 https://www.cnki.com.cn/Article/CJFDTOTAL-LNXG201905030.htm 王兆鹏, 车妍, 袁园, 等. 抑瘤素M在心脏疾病中的研究进展[J]. 中华老年心脑血管病杂志, 2019, 21(5): 548-550.

WANG Z P CHE Y YUAN Y Research progress of oncostatin M in Heart disease Chin J Geriatr Heart Brain Vessel Dis 2019 21 5 548 550 https://www.cnki.com.cn/Article/CJFDTOTAL-LNXG201905030.htm WANG Z P, CHE Y, YUAN Y, et al . Research progress of oncostatin M in Heart disease[J ] . Chin J Geriatr Heart Brain Vessel Dis, 2019, 21(5): 548-550.

International diabetes federation: diabetes atlas IDF, 9th edition [EB/OL ] . Brussels : International Diabetes Federation , 2019 [ 2019-11-14 ] . https://www.diabetesatlas.org . International diabetes federation: diabetes atlas IDF, 9th edition [EB/OL]. Brussels: International Diabetes Federation, 2019[2019-11-14]. https://www.diabetesatlas.org.

WANG P H HUANG B S HORNG H C Wound healing J Chin Med Assoc 2018 81 2 94 101 10.1016/j.jcma.2017.11.002 WANG P H, HUANG B S, HORNG H C, et al . Wound healing[J ] . J Chin Med Assoc, 2018, 81(2): 94-101. DOI: 10.1016/j.jcma.2017.11.002.

ROGNONI E WATT F M Skin cell heterogeneity in development, wound healing, and cancer Trends Cell Biol 2018 28 9 709 722 10.1016/j.tcb.2018.05.002 ROGNONI E, WATT F M. Skin cell heterogeneity in development, wound healing, and cancer[J]. Trends Cell Biol, 2018, 28(9): 709-722. DOI: 10.1016/j.tcb.2018.05.002.

HERGOVITS S MAIS C HAAN C Oncostatin M induces RIG-I and MDA5 expression and enhances the double- stranded RNA response in fibroblasts J Cell Mol Med 2017 21 11 3087 3099 10.1111/jcmm.13221 HERGOVITS S, MAIS C, HAAN C, et al . Oncostatin M induces RIG-I an d MDA5 expression and enhances the double- stranded RNA response in fibroblasts[J ] . J Cell Mol Med, 2017, 21(11): 3087-3099. DOI: 10.1111/jcmm.13221.

STEFAN R J Interleukin-6 family cytokines Cold Spring Harb Perspect Biol 2018 10 2 a028415 10.1101/cshperspect.a028415 STEFAN R J. Interleukin-6 family cytokines[J]. Cold Spring Harb Perspect Biol, 2018, 10(2): a028415. DOI: 10.1101/cshperspect.a028415.

KUROSAWA T YAMADA A TAKAMI M Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways FEBS Open Bio 2015 5 303 307 10.1016/j.fob.2015.04.001 KUROSAWA T, YAMADA A, TAKAMI M, et al . Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways[J ] . FEBS Open Bio, 2015, 5: 303-307. DOI: 10.1016/j.fob.2015.04.001.

ZHANG X MA S ZHANG R Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway Acta Biochim Biophys Sin (Shanghai) 2016 48 3 257 265 10.1093/abbs/gmv137 ZHANG X, MA S, ZHANG R, et al . Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway[J ] . Acta Biochim Biophys Sin (Shanghai), 2016, 48(3): 257-265. DOI: 10.1093/abbs/gmv137.

FRE ' DE ' RIC T GUERTON B ANGINOT A Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications JCI Insight 2017 2 21 e96034 10.1172/jci.insight.96034 FRE ' DE ' RIC T, GUERTON B, ANGINOT A, et al . Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications[J ] . JCI Insight, 2017, 2(21): e96034. DOI: 10.1172/jci.insight.96034.

IMAI K KATO H TAGUCHI Y Biological effects of shikonin in human gingival fibroblasts via ERK 1/2 signaling pathway Molecules 2019 24 19 3542 10.3390/molecules24193542 IMAI K, KATO H, TAGUCHI Y, et al . Biological effects of shikonin in human gingival fibroblasts via ERK 1/2 signaling pathway[J ] . Molecules, 2019, 24(19): 3542. DOI: 10.3390/molecules24193542.

MOZAFFARIAN A BREWER A W TRUEBLOOD E S Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis J Immunol 2008 181 10 7243 7253 10.4049/jimmunol.181.10.7243 MOZAFFARIAN A, BREWER A W, TRUEBLOOD E S, et al . Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis[J ] . J Immunol, 2008, 181(10): 7243-7253. DOI: 10.4049/jimmunol.181.10.7243.

SCAFFIDI A K MUTSAERS S E MOODLEY Y P Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts Br J Pharmacol 2002 136 5 793 801 10.1038/sj.bjp.0704769 SCAFFIDI A K, MUTSAERS S E, MOODLEY Y P, et al . Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts[J ] . Br J Pharmacol, 2002, 136(5): 793-801. DOI: 10.1038/sj.bjp.0704769.

王晓玲 D类细胞周期素在细胞周期中的作用国外医学(分子生物学分册) 2002 1 44 46 https://www.cnki.com.cn/Article/CJFDTOTAL-GWWX200201014.htm 王晓玲. D类细胞周期素在细胞周期中的作用[J]. 国外医学(分子生物学分册), 2002(1): 44-46.

WANG X L Role of class D cyclins in the cell cycle J Mol Biol 2002 24 1 44 46 https://www.cnki.com.cn/Article/CJFDTOTAL-GWWX200201014.htm WANG X L. Role of class D cyclins in the cell cycle[J]. J Mol Biol, 2002; 24((1): 44-46.

CHEN C A CHENG Y C HWANG J C Cyclin D1 expression in podocytes: regulated by mitogens in collaboration with integrin-extracellular matrix interaction through extracellular signal-regulated kinase Exp Biol Med Maywood N J 2012 237 5 516 523 10.1258/ebm.2012.011156 CHEN C A, CHENG Y C, HWANG J C, et al . Cyclin D1 expression in podocytes: regulated by mitogens in collaboration with integrin-extracellular matrix interaction through extracellular signal-regulated kinase[J ] . Exp Biol Med Maywood N J, 2012, 237(5): 516-523. DOI: 10.1258/ebm.2012.011156.

TRACY L E MINASIAN R A CATERSON E J Extra-cellular matrix and dermal fibroblast function in the healing wound Adv Wound Care (New Rochelle) 2016 5 3 119 136 10.1089/wound.2014.0561 TRACY L E, MINASIAN R A, CATERSON E J. Extra-cellular matrix and dermal fibroblast function in the healing wound[J]. Adv Wound Care (New Rochelle), 2016, 5(3): 119-136. DOI: 10.1089/wound.2014.0561.

XUAN Y H HUANG B B TIAN H S High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation PLoS ONE 2014 9 9 e108182 10.1371/journal.pone.0108182 XUAN Y H, HUANG B B, TIAN H S, et al . High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation[J ] . PLoS ONE, 2014, 9(9): e108182. DOI: 10.1371/journal.pone.0108182.

MINOSSI J G LIMA F O CARAMORI C A Alloxan diabetes alters the tensile strength, morphological and morphometric parameters of abdominal wall healing in rats Acta Cir Bras 2014 29 2 118 124 10.1590/S0102-86502014000200008 MINOSSI J G, LIMA F O, CARAMORI C A, et al . Alloxan diabetes alters the tensile strength, morphological and morphometric parameters of abdominal wall healing in rats[J ] . Acta Cir Bras, 2014, 29(2): 118-124. DOI: 10.1590/S0102-86502014000200008.

MAIONE A G SMITH A KASHPUR O Altered ECM deposition by diabetic foot ulcer-derived fibroblasts implicates fibronectin in chronic wound repair Wound Repair Regen 2016 24 4 630 643 10.1111/wrr.12437 MAIONE A G, SMITH A, KASHPUR O, et al . Altered ECM deposition by diabetic foot ulcer-derived fibroblasts implicates fibronectin in chronic wound repair[J ] . Wound Repair Regen, 2016, 24(4): 630-643. DOI: 10.1111/wrr.12437.

BYGD H C AKILBEKOVA D MUÑOZ A Poly-L-arginine based materials as instructive substrates for fibroblast synthesis of collagen Biomaterials 2015 63 47 57 10.1016/j.biomaterials.2015.05.045 BYGD H C, AKILBEKOVA D, MUÑOZ A, et al . Poly-L-arginine based materials as instructive substrates for fibroblast synthesis of collagen[J ] . Biomaterials, 2015, 63: 47-57. DOI: 10.1016/j.biomaterials.2015.05.045.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

miR-186-5p负性调控CDCA3对高脂高糖诱导的胰岛β细胞具有保护作用

胎盘间充质干细胞外泌体对高糖培养的成纤维细胞衰老的影响

阻断TGF-β/TGF-βRⅠ通路对ATDC5细胞增殖、分化及细胞外基质的影响

超低浓度二甲基亚砜促进皮肤成纤维细胞增殖作用及机制研究

谷胱甘肽过氧化物酶7通过PI3K-AKT通路调控肝癌细胞增殖和衰老