PKC promotes proliferation of airway smooth muscle cells by regulating cyclinD1 expression in asthmatic rats1
Li-fen QIAO
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorCorresponding Author
Yong-jian XU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Correspondence to Prof Yong-jian XU. Phn 86-27-8366-2176. Fax 86-27-8366-2898. E-mail [email protected]Search for more papers by this authorXian-sheng LIU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJun-gang XIE
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJin WANG
Department of Emergency Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorChun-ling DU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJian ZHANG
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorWang NI
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorShi-xin CHEN
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorLi-fen QIAO
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorCorresponding Author
Yong-jian XU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Correspondence to Prof Yong-jian XU. Phn 86-27-8366-2176. Fax 86-27-8366-2898. E-mail [email protected]Search for more papers by this authorXian-sheng LIU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJun-gang XIE
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJin WANG
Department of Emergency Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorChun-ling DU
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorJian ZHANG
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorWang NI
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorShi-xin CHEN
Department of Respiratory Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Search for more papers by this authorThis work was supported by the National Natural Science Foundation of China (No 3067092).
Abstract
Aim: To determine whether protein kinase C (PKC) has any effect on the expression of cyclinD1, a key regulator of growth control and G/S transition, and to investigate the underlying molecular mechanisms of PKC involving the remodeling of the asthmatic airway smooth muscle (ASM). Methods: The treatment of synchronized ASM cells from asthmatic rats with PKC-specific agonist phorbol 12-myristate 13-acetate (PMA) and antagonist 2-{1-[3-(amidinothio) propyl]-1H-indol-3-yl}-3-(1-methylindol-3-yl) maleimide methanesulfonate salt (Ro31-8220) was followed by the proliferation assay. PKCα and cyclinD1 expressions in ASM cells (ASMC) were detected by RT-PCR and Western blotting. The relation between PKCα and cyclinD1 was assessed by linear regression analysis. The effect of the construct recombinant plasmid pcDNA3.1-antisense cyclinD1 (pcDNA3.1-ascyclinD1) on the proliferation of ASMC was found to be induced by PMA. Results: The data showed phorbol ester-dependent PKCα promoted the proliferation of ASMC. The closely-positive correlation existed between the expression of PKCα and cyclinD1 at the transcriptional (r=0.821, P<0.01) and transla-tional (r=0.940, P<0.01) levels. pcDNA3.1-ascyclinD1 could inhibit the proliferation of ASMC. pcDNA3.1-ascyclinD1 almost completely attenuated the PMA-induced proliferation effect as Ro31-8220+pcDNA3.1. Conclusion: The proliferation of ASMC by PKC might by regulated by the cyclinD expression in asthmatic rats.
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