PTEN gene silencing contributes to airway remodeling and induces airway smooth muscle cell proliferation in mice with allergic asthma
Authors: Li-Fang Liu
Dong-Mei Wu
Xin-Rui Han
Xin Wen
Jing Yan
Jun Lu
Gui-Hong Zheng
Ran Tang
Yuan-Lin Zheng
Journal: Journal of thoracic disease (2018)
Discipline: CLINICAL MEDICINE
Keywords: Phosphatase and tensin homolog (PTEN); airway remodeling; airway smooth muscle cell (ASMC); alpha smooth muscle actin; asthma
Affiliations: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China., College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, China., Emergency Center, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221009, China., Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China.

Abstract:  Background: Allergic asthma is a complex genetic disorder that involves interactions between genetic and environmental factors. Usage of PTEN may be a good therapeutic strategy for the management of allergic inflammation. Thus, the present study aims to explore the effects of phosphatase and tensin homolog (PTEN) gene silencing on airway remodeling and proliferation of airway smooth muscle cells (ASMCs) in a mouse model of allergic asthma. Methods: A total of 56 healthy female BABL/c mice (weighing between 16 to 22 grams) were selected and were assigned on random into ovalbumin (OVA; mice were stimulated with OVA to induce allergic asthma), OVA + si-PTEN, normal saline (NS; mice were treated with normal saline) and NS + si-PTEN groups. Masson staining was employed in order to observe lung tissue sections. Immunohistochemical staining was used to detect the expression of α-SMA+. Gene silencing was conducted in the NS + si-PTEN and OVA + si-PTEN groups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to detect the mRNA and protein expressions of PTEN in ASMCs of each group. CCK-8 assay and flow cytometry were performed to determine the cell proliferation rate and cell cycle. Results: Airway remodeling and changes of smooth muscle layer were found in allergic asthmatic mice with thick airway walls. The expression of alpha smooth muscle actin (α-SMA+) was significantly higher in ASMCs of the OVA, OVA + si-PTEN and NS + si-PTEN groups compared with ASMCs of the NS group. The mRNA and protein expressions of PTEN reduced in the OVA, OVA + si-PTEN and NS + si-PTEN groups. The rate of ASMCs proliferation in OVA, OVA + si-PTEN and NS + si-PTEN groups were significantly higher than the NS group. The proportion of ASMCs in S and G2 stages increased, while the number of cells in the G1 stage decreased after PTEN gene silencing. Conclusions: These results demonstrated that PTEN gene silencing might promote proliferation of ASMCs and airway remodeling in a mouse model of allergic asthma. 

Retracted: No

PubPeer comments:
  Figure 3 Protein expression of PTEN in airway smooth muscle cells of mice in each group. (A) Gray value of PTEN protein . ![file] This is a versatile loading control. Some other roles: Fig 6B from [Han et al (2018)] .  Overexpressed miRu2010140u20105p inhibits the expression of Wnt1 in 293FT cells by RT u2010qPCR and Western blot analysis.... B, the histogram of the protein expression of Wnt1 and corresponding protein bands . ![] Fig. 4 from [Zhang et al (2018)] .  The expression of LINC00652 and the mRNA and protein levels of GLP-1R in the myocardium of mice after myocardial I R were increased. ... Panel C, GLP-1R protein in the myocardium of mice measured by western blotting before and after modeling . ![] Below at left, Fig. 6B from [Zhou et al (2018)] .  ELISA and western blot analysis were applied to determine the miR- 495 expression and mRNA and protein expression of NLRP3, TNF-u03b1, IL-1u03b2, IL-18 and caspase-1. At right, Fig 11E from [Wang et al (2018)] .  E: protein bands of each factor in ASMCs of asthma mice in each group detected by western blot analysis . ![] , 
 Assessed here, as part of the first of 10 broad investigations: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- About the existence of papers published on Wu Dongmei, Zheng Yuanlin, Lu Jun, etc. - Falsification of pictures or data, fabrication of research process, use of others signatures without consent, and false information in project final reports - processing decision - National Science and Technology Financial Supervisory Office [2022] No. 1 u3000u3000The Supervision Committee of the National Natural Science Foundation of China launched an investigation into several papers of Jiangsu Normal University, including Wu Dongmei, Zheng Yuanlin, and Jun Jun, for suspected academic misconduct. The papers involved are as follows: ... u3000u3000Paper 3:  Xin Wen # , Jing Yan # , Xin-Rui Han # , Gui-Hong Zheng, Ran Tang, Li-Fang Liu, Dong-Mei Wu, Jun Lu*, Yuan-Lin Zheng*. **PTEN gene silencing contributes to airway remodeling and induces airway smooth muscle cell proliferation in mice with allergic asthma**. Journal of Thoracic Disease, 2018, 10(1):202-211.u201d (with fund numbers 81271225, 31201039, 81171012, 30950031, 81571055, 81400902) ... u3000u3000According to the investigation of the supporting unit, the above 35 papers involved all have the problem of improper use of pictures or data fraud, and the pictures or data in question are all provided by third-party companies. Among the 35 papers involved, 34 (except paper 21) still have the problem of using others signatures without consent, and papers 4, 5, 9, 12, 30, and 34 also have the problem of fabricating the research process. Wu Dongmei is the author of the above 35 papers involved, of which 12 papers (papers 2, 8, 9, 10, 11, 12, 14, 15, 25, 26, 30, 35) are the first author and 22 papers (Paper 1, 4, 5, 6, 7, 13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 27, 28, 29, 31, 32, 33, 34) Corresponding author, They should be primarily responsible for the objective results of falsifying pictures or data, using others signatures without consent, and fabricating research processes; Zheng Yuanlin and Lu Jun, as the co-corresponding authors of the 35 papers involved, were negligent in reviewing and took secondary responsibility. In addition, Wu Dongmei included 4 papers involved (papers 21, 24, 28, 29) in the final report of the National Natural Science Foundation of China (Grant No. 81400902), and Zheng Yuanlin included 9 papers involved (papers 6, 8, 10, 13, 21, 24, 26, 28, 29) included in the final report of the National Natural Science Foundation of China (Grant No. 81571055), and should be responsible for the objective results of false information in the final report. u3000u3000After deliberation at the 12th meeting of the Fifth Supervision Committee of the National Natural Science Foundation of China (Life Medicine Professional Committee) and the approval of the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to follow the thirty-fifth National Natural Science Foundation of China Regulations. Article 4, Article 17, Items 3, 4, and 9 of  Measures for Handling Misconduct in Science Fund Work by the Supervision Committee of the National Natural Science Foundation of China (for Trial Implementation) , revocation of Wu Dongmei s National Natural Science Foundation of Molecular mechanism of TRPV4-mediated domoic acid treatment-induced cognitive deficits in mice (Grant No. 81400902), recovering the allocated funds, permanently disqualifying Wu Dongmei from the National Natural Science Foundation of China (since January 18, 2022), Give Wu Dongmei a circular of criticism; decide to follow Article 35, item 4 of the  National Natural Science Foundation of China Regulations , and refer to  The National Natural Science Foundation of China Supervision Committee s Handling of Misconduct in Science Fund Work (Trial) Tenth Items 3 and 4 of seven articles, the Zheng Yuanlin National Natural Science Foundation of China project  The Mechanism of HDAC6 Activating HMGB1 RAGE Signaling Axis to Mediate Cognitive Defects in Type 2 Diabetic Mice (Approval No. 81571055), recover the allocated funds, cancel Zheng Yuanlin will be eligible to apply for the National Natural Science Foundation of China for 5 years (January 18, 2022 to January 17, 2027), and will give Zheng Yuanlin a notice of criticism; it is decided to refer to the  National Natural Science Foundation of China Supervision Committee on misconduct in the work of the National Natural Science Foundation of China. Items 3 and 4 of Article 17 of the Measures (for Trial Implementation), the Army s National Natural Science Foundation of China project application qualification will be cancelled for 5 years (January 18, 2022 to January 17, 2027), and the Army will be criticized in a circular. - National Natural Science Foundation of China - March 30, 2022 ,