{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:58:44Z","timestamp":1785376724062,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31790411"],"award-info":[{"award-number":["31790411"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672508"],"award-info":[{"award-number":["31672508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31372397"],"award-info":[{"award-number":["31372397"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      This study aimed to investigate the effects of exogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S on the proliferation of porcine mammary gland epithelial cells (PMECs) and explore the underlying mechanisms. We found that exposure of PMECs to NaHS, at concentrations ranging from 10 to 200\u2009\u00b5M, stimulated cell proliferation. However, high concentration of NaHS (600\u2009\u00b5M) inhibited PMECs proliferation. Accordingly, 10\u2009\u00b5M NaHS significantly increased the percentage of cells undergoing DNA replication, elevated the mRNA and\/or protein expression of Cyclin A2, Cyclin D1\/3, Cyclin E2 and PCNA, and decreased p21 mRNA expression. In contrast, 600\u2009\u00b5M NaHS elicited the opposite effects to that of 10\u2009\u00b5M NaHS. In addition, PI3\u2009K\/Akt and mTOR signaling pathways were activated or inhibited in response to 10 or 600\u2009\u00b5M NaHS, respectively. Furthermore, the promotion of PMECs proliferation, the change of proliferative genes expression, and the activation of mTOR signaling pathway induced by 10\u2009\u00b5M NaHS were effectively blocked by PI3\u2009K inhibitor Wortmannin. Similarly, inhibition of mTOR with Rapamycin totally abolished the 10\u2009\u00b5M NaHS\u2010induced stimulation of PMECs proliferation and alteration of proliferative genes expression, with no influence on PI3\u2009K\/Akt signaling pathway. Moreover, constitutive activation of Akt pathway via transfection of Akt\u2010CA completely eliminated the inhibition of PMECs proliferation and mTOR signaling pathway, and the change of proliferative genes expression induced by 600\u2009\u00b5M NaHS. In conclusion, our findings provided evidence that exogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S supplied by NaHS exerted biphasic effects on PMECs proliferation, with stimulation at lower doses and suppression at high dose, through the intracellular PI3\u2009K\/Akt\u2010mTOR signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26630","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T03:06:51Z","timestamp":1525921611000},"page":"7071-7081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Exogenous H\n                    <sub>2<\/sub>\n                    S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K\/Akt\u2010mTOR signaling pathway"],"prefix":"10.1002","volume":"233","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Ye","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Fu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Shu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-9401","authenticated-orcid":false,"given":"Songbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University  Guangzhou P. R. China"},{"name":"National Engineering Research Center for Breeding Swine Industry South China Agricultural University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2007-0726"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309937200"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20090368"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.199919"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-animal-031412-103632"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.031"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12609"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2015-9250"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.10.019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4141\/cjas2012-066"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3920\/978-90-8686-803-2_4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000350097"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-014-0530-7"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90499-G"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3221"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157237"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-008-0151-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574362409666140206222746"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.08.130"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.091744"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2013.11.009"},{"key":"e_1_2_8_24_1","first-page":"1183","article-title":"GYY4137 stimulates osteoblastic cell proliferation and differentiation via an ERK1\/2\u2010dependent anti\u2010oxidant mechanism","volume":"9","author":"Lv M.","year":"2017","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902952106"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.07.044"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.07.075"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.6b04878"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.08.023"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2010.223"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.126714"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186245"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908047106"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.1509.09051"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-016-0078-8"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.12.015"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00294.2015"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2011"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.18"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.5048"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100454"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037572"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2017.04.010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6570671"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4691"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.26630","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.26630","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.26630","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.26630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:19:10Z","timestamp":1785374350000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.26630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/jcp.26630"],"URL":"https:\/\/doi.org\/10.1002\/jcp.26630","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,10]]},"assertion":[{"value":"2017-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}