Hydrogen Sulfide Improves Wound Healing via Restoration of Endothelial Progenitor Cell Functions and Activation of Angiopoietin-1 in Type 2 Diabetes

Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabe...

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Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2014-05, Vol.63 (5), p.1763-1778
Hauptverfasser: FANG LIU, CHEN, Dan-Dan, XIN SUN, XIE, He-Hui, HONG YUAN, JIA, Wei-Ping, CHEN, Alex F
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container_issue 5
container_start_page 1763
container_title Diabetes (New York, N.Y.)
container_volume 63
creator FANG LIU
CHEN, Dan-Dan
XIN SUN
XIE, He-Hui
HONG YUAN
JIA, Wei-Ping
CHEN, Alex F
description Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.
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Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. 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Target tissue resistance ; Hydrogen sulfide ; Hydrogen Sulfide - pharmacology ; Hydrogen Sulfide - therapeutic use ; Medical sciences ; Mice ; Neovascularization, Physiologic - drug effects ; Protein expression ; Stem Cells - drug effects ; Stem Cells - metabolism ; Wound healing ; Wound Healing - drug effects</subject><ispartof>Diabetes (New York, N.Y.), 2014-05, Vol.63 (5), p.1763-1778</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright American Diabetes Association May 2014</rights><rights>2014 by the American Diabetes Association. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-af416beb75242c3a4fa8fda465881730b2ddfe9ce39cf1a821da0508fc5a96513</citedby><cites>FETCH-LOGICAL-c499t-af416beb75242c3a4fa8fda465881730b2ddfe9ce39cf1a821da0508fc5a96513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994958/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994958/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=28496765$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24487028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FANG LIU</creatorcontrib><creatorcontrib>CHEN, Dan-Dan</creatorcontrib><creatorcontrib>XIN SUN</creatorcontrib><creatorcontrib>XIE, He-Hui</creatorcontrib><creatorcontrib>HONG YUAN</creatorcontrib><creatorcontrib>JIA, Wei-Ping</creatorcontrib><creatorcontrib>CHEN, Alex F</creatorcontrib><title>Hydrogen Sulfide Improves Wound Healing via Restoration of Endothelial Progenitor Cell Functions and Activation of Angiopoietin-1 in Type 2 Diabetes</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. 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Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.</description><subject>Angiogenesis</subject><subject>Angiopoietin-1 - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Complications</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Disease Models, Animal</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Hydrogen sulfide</subject><subject>Hydrogen Sulfide - pharmacology</subject><subject>Hydrogen Sulfide - therapeutic use</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Protein expression</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcuKFDEUhoMoTju68AUkIC5clOZWlWQjNO2MPTCg6IjuQiqXngzVSZlUNfR7-MCmnbZVskjgfPnO4fwAPMfoDaGUv7U9pg1igj4ACyypbCjh3x-CBUKYNJhLfgaelHKHEOrqeQzOCGOCIyIW4Od6b3PauAi_zIMP1sGr7ZjTzhX4Lc3RwrXTQ4gbuAsafnZlSllPIUWYPLyINk23bgh6gJ9-S0Itw5UbBng5R3PgCtRVsqzv3enfMm5CGlNwU4gNhiHCm_3oIIHvg-7d5MpT8Mjrobhnx_scfL28uFmtm-uPH65Wy-vGMCmnRnuGu971vCWMGKqZ18JbzbpWCMwp6om13knjqDQea0Gw1ahFwptWy67F9By8u_eOc7911rg4ZT2oMYetznuVdFD_V2K4VZu0U1RKJltRBS-Pgpx-zHU76i7NOdaZFe4o76hEklfq9T1lciolO3_qgJE6BKgOAapDgJV98e9IJ_JPYhV4dQR0MXrwWUcTyl9OMNnxrqW_AD7Rpjc</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>FANG LIU</creator><creator>CHEN, Dan-Dan</creator><creator>XIN SUN</creator><creator>XIE, He-Hui</creator><creator>HONG YUAN</creator><creator>JIA, Wei-Ping</creator><creator>CHEN, Alex F</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope></search><sort><creationdate>20140501</creationdate><title>Hydrogen Sulfide Improves Wound Healing via Restoration of Endothelial Progenitor Cell Functions and Activation of Angiopoietin-1 in Type 2 Diabetes</title><author>FANG LIU ; CHEN, Dan-Dan ; XIN SUN ; XIE, He-Hui ; HONG YUAN ; JIA, Wei-Ping ; CHEN, Alex F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-af416beb75242c3a4fa8fda465881730b2ddfe9ce39cf1a821da0508fc5a96513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Angiogenesis</topic><topic>Angiopoietin-1 - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Complications</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes. 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Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>24487028</pmid><doi>10.2337/db13-0483</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete; PubMed Central
subjects Angiogenesis
Angiopoietin-1 - metabolism
Animals
Biological and medical sciences
Complications
Diabetes
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - metabolism
Diabetes. Impaired glucose tolerance
Disease Models, Animal
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelium
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Hydrogen sulfide
Hydrogen Sulfide - pharmacology
Hydrogen Sulfide - therapeutic use
Medical sciences
Mice
Neovascularization, Physiologic - drug effects
Protein expression
Stem Cells - drug effects
Stem Cells - metabolism
Wound healing
Wound Healing - drug effects
title Hydrogen Sulfide Improves Wound Healing via Restoration of Endothelial Progenitor Cell Functions and Activation of Angiopoietin-1 in Type 2 Diabetes
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