Evidence That ADAM17 Mediates the Protective Action of CGRP against Angiotensin II-Induced Inflammation in Vascular Smooth Muscle Cells. 2018

Si-Yu Zeng, and Li Yang, and Chen-Liang Hong, and Hui-Qin Lu, and Qiu-Jiang Yan, and Yan Chen, and Xu-Ping Qin
Institution of Drug Clinical Trial, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.

Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D012084 Renin-Angiotensin System A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM. Renin-Angiotensin-Aldosterone System,Renin Angiotensin Aldosterone System,Renin Angiotensin System,System, Renin-Angiotensin,System, Renin-Angiotensin-Aldosterone
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000072198 ADAM17 Protein A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. It cleaves several other CELL SURFACE PROTEINS, including INTERLEUKIN-1 RECEPTOR TYPE II; TRANSFORMING GROWTH FACTOR ALPHA; L-SELECTIN; MUCIN-1; and AMYLOID BETA-PROTEIN PRECURSOR. It can also function as an activator of the Notch signaling pathway by mediating the cleavage of NOTCH RECEPTORS. ADAM-17,ADAM-17 Protein,CD156b Antigen,Disintegrin and Metalloproteinase Domain-Containing Protein 17,TACA (Enzyme),TACE (Enzyme),TNF-alpha Convertase,TNF-alpha Converting Enzyme,Tumor Necrosis Factor Alpha Convertase,Tumor Necrosis Factor-alpha Convertase,Tumor Necrosis Factor-alpha Converting Enzyme,ADAM 17 Protein,Antigen, CD156b,Convertase, TNF-alpha,Disintegrin and Metalloproteinase Domain Containing Protein 17,TNF alpha Convertase,TNF alpha Converting Enzyme,Tumor Necrosis Factor alpha Converting Enzyme
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015740 Calcitonin Gene-Related Peptide A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Calcitonin Gene-Related Peptide I,Calcitonin Gene-Related Peptide II,alpha-CGRP,alpha-Calcitonin Gene-Related Peptide,beta-CGRP,beta-Calcitonin Gene-Related Peptide,Calcitonin Gene Related Peptide,Calcitonin Gene Related Peptide I,Calcitonin Gene Related Peptide II,Gene-Related Peptide, Calcitonin,alpha Calcitonin Gene Related Peptide,beta Calcitonin Gene Related Peptide
D048052 Mitogen-Activated Protein Kinase 3 A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS. Extracellular Signal-Regulated Kinase 1,ERK1 Kinase,MAPK3 Mitogen-Activated Protein Kinase,Meiosis-Activated Myelin Basic Protein Kinase p44(mpk),Microtubule-Associated Protein-2 Kinase,PSTkinase p44mpk,Protein-Serine-Threonine Kinase p44(mpk),p44 MAPK,Extracellular Signal Regulated Kinase 1,Kinase, ERK1,Kinase, Microtubule-Associated Protein-2,MAPK3 Mitogen Activated Protein Kinase,Microtubule Associated Protein 2 Kinase,Mitogen Activated Protein Kinase 3,p44mpk, PSTkinase
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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