Literature DB >> 27847966

Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.

Ming-Jer Hsieh1,2, Hsien-Ta Liu1,3,4, Chao-Nin Wang5, Hsiu-Yun Huang1, Yuling Lin1, Yu-Shien Ko2, Jong-Shyan Wang6, Vincent Hung-Shu Chang7, Jong-Hwei S Pang8,9.   

Abstract

BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. KEY MESSAGE: BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.

Entities:  

Keywords:  Angiogenesis; BPC 157; CAM assay; Hind limb ischemia; Tube formation; VEGFR2

Mesh：

Substances：

Year:  2016        PMID： 27847966     DOI： 10.1007/s00109-016-1488-y

Source DB:  PubMed          Journal:  J Mol Med (Berl)        ISSN： 0946-2716            Impact factor:   4.599


  42 in total

1.  Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial.

Authors:  Robert J Lederman; Farrell O Mendelsohn; R David Anderson; Jorge F Saucedo; Alan N Tenaglia; James B Hermiller; William B Hillegass; Krishna Rocha-Singh; Thomas E Moon; M J Whitehouse; Brian H Annex
Journal:  Lancet       Date:  2002-06-15       Impact factor: 79.321

Review 2.  Stable gastric pentadecapeptide BPC 157-NO-system relation.

Authors:  Predrag Sikiric; Sven Seiwerth; Rudolf Rucman; Branko Turkovic; Dinko Stancic Rokotov; Luka Brcic; Marko Sever; Robert Klicek; Bozo Radic; Domagoj Drmic; Spomenko Ilic; Danijela Kolenc; Gorana Aralica; Mirjana Stupnisek; Jelena Suran; Ivan Barisic; Senka Dzidic; Hrvoje Vrcic; Bozidar Sebecic
Journal:  Curr Pharm Des       Date:  2014       Impact factor: 3.116

3.  Antiinflammatory effect of BPC 157 on experimental periodontitis in rats.

Authors:  B Keremi; Z Lohinai; P Komora; S Duhaj; K Borsi; G Jobbagy-Ovari; K Kallo; A D Szekely; A Fazekas; C Dobo-Nagy; P Sikiric; G Varga
Journal:  J Physiol Pharmacol       Date:  2009-12       Impact factor: 3.011

Review 4.  A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC.

Authors:  P Sikirić; M Petek; R Rucman; S Seiwerth; Z Grabarević; I Rotkvić; B Turković; V Jagić; B Mildner; M Duvnjak
Journal:  J Physiol Paris       Date:  1993

5.  Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2.

Authors:  Ichiro Masaki; Yoshikazu Yonemitsu; Akihisa Yamashita; Shihoko Sata; Mitsugu Tanii; Kimihiro Komori; Kazunori Nakagawa; Xiaogang Hou; Yoshiyuki Nagai; Mamoru Hasegawa; Keizo Sugimachi; Katsuo Sueishi
Journal:  Circ Res       Date:  2002-05-17       Impact factor: 17.367

6.  Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse.

Authors:  Martina Lovric-Bencic; Predrag Sikiric; Jadranka S Hanzevacki; Sven Seiwerth; Dunja Rogic; Vesna Kusec; Gorana Aralica; Pasko Konjevoda; Lovorka Batelja; Alenka B Blagaic
Journal:  J Pharmacol Sci       Date:  2004-05       Impact factor: 3.337

7.  Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression.

Authors:  Vanesa Ivetić Tkalcević; Snjezana Cuzić; Karmen Brajsa; Boris Mildner; Ana Bokulić; Kristina Situm; Daniela Perović; Ines Glojnarić; Michael J Parnham
Journal:  Eur J Pharmacol       Date:  2007-06-16       Impact factor: 4.432

8.  VEGFR2 trafficking: speed doesn't kill.

Authors:  Xi Zhang; Anthony A Lanahan; Michael Simons
Journal:  Cell Cycle       Date:  2013-07-15       Impact factor: 4.534

9.  Treatment of mouse limb ischemia with an integrative hypoxia-responsive vector expressing the vascular endothelial growth factor gene.

Authors:  Eduardo Gallatti Yasumura; Roberta Sessa Stilhano; Vívian Yochiko Samoto; Priscila Keiko Matsumoto; Leonardo Pinto de Carvalho; Valderez Bastos Valero Lapchik; Sang Won Han
Journal:  PLoS One       Date:  2012-03-21       Impact factor: 3.240

10.  Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

Authors:  Chung-Hsun Chang; Wen-Chung Tsai; Ya-Hui Hsu; Jong-Hwei Su Pang
Journal:  Molecules       Date:  2014-11-19       Impact factor: 4.411
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  25 in total

1.  Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

Authors:  Krešimir Luetic; Mario Sucic; Josipa Vlainic; Zeljka Belosic Halle; Dean Strinic; Tinka Vidovic; Franka Luetic; Marinko Marusic; Sasa Gulic; Tatjana Turudic Pavelic; Antonio Kokot; Ranka Serventi Seiwerth; Domagoj Drmic; Lovorka Batelja; Sven Seiwerth; Predrag Sikiric
Journal:  Inflammopharmacology       Date:  2017-03-02       Impact factor: 4.473

2.  Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats.

Authors:  Ivan Maria Smoday; Igor Petrovic; Luka Kalogjera; Hrvoje Vranes; Helena Zizek; Ivan Krezic; Slaven Gojkovic; Ivan Skorak; Klaudija Hriberski; Ivan Brizic; Milovan Kubat; Sanja Strbe; Ivan Barisic; Marija Sola; Eva Lovric; Marin Lozic; Alenka Boban Blagaic; Anita Skrtic; Sven Seiwerth; Predrag Sikiric
Journal:  Biomedicines       Date:  2022-06-01

3.  Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy.

Authors:  Darko Perovic; Marija Milavic; Stjepan Dokuzovic; Ivan Krezic; Slaven Gojkovic; Hrvoje Vranes; Igor Bebek; Vide Bilic; Nenad Somun; Ivan Brizic; Ivan Skorak; Klaudija Hriberski; Suncana Sikiric; Eva Lovric; Sanja Strbe; Milovan Kubat; Alenka Boban Blagaic; Anita Skrtic; Sven Seiwerth; Predrag Sikiric
Journal:  Curr Issues Mol Biol       Date:  2022-04-27       Impact factor: 2.976

4.  Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

Authors:  Zeljka Belosic Halle; Josipa Vlainic; Domagoj Drmic; Dean Strinic; Kresimir Luetic; Mario Sucic; Maria Medvidovic-Grubisic; Tatjana Pavelic Turudic; Igor Petrovic; Sven Seiwerth; Predrag Sikiric
Journal:  Inflammopharmacology       Date:  2017-05-17       Impact factor: 4.473

5.  Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion.

Authors:  Marijan Kolovrat; Slaven Gojkovic; Ivan Krezic; Dominik Malekinusic; Borna Vrdoljak; Katarina Kasnik Kovac; Tamara Kralj; Domagoj Drmic; Ivan Barisic; Katarina Horvat Pavlov; Andreja Petrovic; Antonija Duzel; Mario Knezevic; Ivan Mirkovic; Antonio Kokot; Alenka Boban Blagaic; Sven Seiwerth; Predrag Sikiric
Journal:  World J Hepatol       Date:  2020-05-27

6.  Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights.

Authors:  Antonija Duzel; Josipa Vlainic; Marko Antunovic; Dominik Malekinusic; Borna Vrdoljak; Mariam Samara; Slaven Gojkovic; Ivan Krezic; Tinka Vidovic; Zdenko Bilic; Mario Knezevic; Marko Sever; Nermin Lojo; Antonio Kokot; Marijan Kolovrat; Domagoj Drmic; Jaksa Vukojevic; Tamara Kralj; Katarina Kasnik; Marko Siroglavic; Sven Seiwerth; Predrag Sikiric
Journal:  World J Gastroenterol       Date:  2017-12-28       Impact factor: 5.742

Review 7.  Stable Gastric Pentadecapeptide BPC 157 and Wound Healing.

Authors:  Sven Seiwerth; Marija Milavic; Jaksa Vukojevic; Slaven Gojkovic; Ivan Krezic; Lovorka Batelja Vuletic; Katarina Horvat Pavlov; Andrea Petrovic; Suncana Sikiric; Hrvoje Vranes; Andreja Prtoric; Helena Zizek; Tajana Durasin; Ivan Dobric; Mario Staresinic; Sanja Strbe; Mario Knezevic; Marija Sola; Antonio Kokot; Marko Sever; Eva Lovric; Anita Skrtic; Alenka Boban Blagaic; Predrag Sikiric
Journal:  Front Pharmacol       Date:  2021-06-29       Impact factor: 5.810

8.  BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats.

Authors:  Mirna Zlatar; Antonio Kokot; Lovorka Batelja Vuletic; Sanja Masnec; Tamara Kralj; Marija Milkovic Perisa; Ivan Barisic; Bozo Radic; Kristina Milanovic; Domagoj Drmic; Sven Seiwerth; Predrag Sikiric
Journal:  Front Pharmacol       Date:  2021-06-10       Impact factor: 5.810

9.  Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

Authors:  Ivan Mirković; Tamara Kralj; Marin Lozić; Vasilije Stambolija; Josip Kovačević; Luka Vrdoljak; Mirna Zlatar; Kristina Milanović; Domagoj Drmić; Jurica Predović; Sanja Masnec; Matija Jurjević; Mladen Bušić; Sven Seiwerth; Antonio Kokot; Predrag Sikirić
Journal:  Acta Clin Croat       Date:  2020-09       Impact factor: 0.780

10.  Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension.

Authors:  Mario Knezevic; Slaven Gojkovic; Ivan Krezic; Helena Zizek; Dominik Malekinusic; Borna Vrdoljak; Hrvoje Vranes; Tamara Knezevic; Ivan Barisic; Katarina Horvat Pavlov; Domagoj Drmic; Miro Staroveski; Antonija Djuzel; Zoran Rajkovic; Toni Kolak; Ivica Kocman; Eva Lovric; Marija Milavic; Suncana Sikiric; Ante Tvrdeic; Leonardo Patrlj; Sanja Strbe; Antonio Kokot; Alenka Boban Blagaic; Anita Skrtic; Sven Seiwerth; Predrag Sikiric
Journal:  Biomedicines       Date:  2021-05-26
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