title: Lung damage induced by hyperglycemia in diabetic rats: The role of signal transducer and activator of transcription 3 (STAT3).
abstract: Increased evidence has shown that diabetes can be a risk factor for pulmonary fibrosis. The objective of this study was to use streptozotocin-induced diabetic rats (STZ rats) to assess the possible signals associated with lung damage in diabetic disorders. The expression levels of signal transducer and activator of transcription 3 (STAT3) and connective tissue growth factor (CTGF) in lung tissues were measured through Western blot analysis and real-time PCR. Additionally, the potential mechanisms were confirmed in cultured rat lung cell line (L2) incubated in high-glucose (HG) medium to mimic the in vivo changes. The pathological changes in the lung tissues of STZ rats were characterized using the bleomycin-treated tissues as reference. Moreover, the higher expression levels of STAT3 and CTGF in the lung tissues of STZ rats were reversed by treating the hyperglycemia. CTGF expression increased following the higher expression of STAT3 in the cultured L2 cells exposed to HG, and this change was reversed by siRNA treatment specific for STAT3. Stattic, at a dose sufficient to inhibit STAT3, reduced the CTGF levels in the lungs of STZ rats. In conclusion, STAT3 enhanced CTGF expression in a type-1 diabetes model associated with lung damage. Thus, STAT3 inhibitors may be developed to improve diabetes-induced lung damage in the future.
authors.affiliation: Chest Division, Department of Internal Medicine, Chi Mei Medical Center- Liouying, Liouying, Tainan City, Taiwan 73601.
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung City, Taiwan 82401.
authors.forename: Chao-Tien
authors.initials: CT
authors.lastname: Hsu
authors.affiliation: Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, Taiwan 97005.
authors.forename: Ho-Shan
authors.initials: HS
authors.lastname: Niu
authors.affiliation: Department of Neurosurgery, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan 71003; Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan 71003.
authors.forename: Chin-Hong
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan 71003; Institute of Medical Sciences, Chang Jung Christian University, Gueiren, Tainan City, Taiwan 71101. Electronic address: jtcheng@mail.cjcu.edu.tw.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan 71003. Electronic address: shieh225@ms29.hinet.net.
authors.forename: Jiunn-Min
authors.initials: JM
authors.lastname: Shieh
mesh_terms: D000818:Animals; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D011658:Pulmonary Fibrosis / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013311:Streptozocin
chemical_list: C526316:CCN2 protein, rat; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D055513:Connective Tissue Growth Factor; D013311:Streptozocin
keywords: CTGF; Hyperglycemia; Lung fibrosis; STAT3; STZ rat; Type-1 diabetes