Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/β-catenin signaling pathway

Gu, Lei; Li, Anmao; Lin, Jing; Gan, Yiling; He, Chunyan; Xiao, Rui; Liao, Jiaxin; Li, Yishi; Guo, Shuliang

doi:10.1007/s00109-022-02261-9

Cited by 8 publications

(3 citation statements)

References 23 publications

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“…Elevated SOX9 levels have also been reported in IPF fibroblasts and tissues, as well as murine fibroblasts in a TGF-α-induced model of PF [36]. Our observed upregulation of SOX9 in SSc lung thus highlights its significance to PF and extends the emerging literature implicating SOX9 in multiple types of fibrosis, including tracheal, liver, cardiac, kidney, and lung [36,[77][78][79][80][81]. A recent RNA sequencing analysis of skin biopsies and peripheral blood mononuclear cells from SSc patients identified the non-coding RNA SOX9-AS1 as a central node in a network of genes correlated with clinical features of SSc, including modified Rodnan skin thickness score, local skin score, forced vital capacity and diffusing capacity for carbon monoxide [82].…”

Section: Sox9 In Pulmonary Fibrosissupporting

confidence: 78%

The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis

Waldrep

Rodgers

Garrett

et al. 2023

IJMS

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Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth factor-II (IGF-II) is overexpressed in lung tissues and fibroblasts from SSc patients, and IGF-II fosters fibrosis by upregulating collagen type I, fibronectin, and TGFβ. We now show that IGF-II augments mRNA levels of profibrotic signaling molecules TGFβ2 (p ≤ 0.01) and TGFβ3 (p ≤ 0.05), collagen type III (p ≤ 0.01), and the collagen posttranslational modification enzymes P4HA2 (p ≤ 0.05), P3H2 (p ≤ 0.05), LOX (p = 0.065), LOXL2 (p ≤ 0.05), LOXL4 (p ≤ 0.05) in primary human lung fibroblasts. IGF-II increases protein levels of TGFβ2 (p ≤ 0.01), as well as COL3A1, P4HA2, P4Hβ, and LOXL4 (p ≤ 0.05). In contrast, IGF-II decreases mRNA levels of the collagen degradation enzymes cathepsin (CTS) K, CTSB, and CTSL and protein levels of CTSK (p ≤ 0.05). The SRY-box transcription factor 9 (SOX9) is overexpressed in SSc lung tissues at the mRNA (p ≤ 0.05) and protein (p ≤ 0.01) levels compared to healthy controls. IGF-II induces SOX9 in lung fibroblasts (p ≤ 0.05) via the IGF1R/IR hybrid receptor, and SOX9 regulates TGFβ2 (p ≤ 0.05), TGFβ3 (p ≤ 0.05), COL3A1 (p ≤ 0.01), and P4HA2 (p ≤ 0.001) downstream of IGF-II. Our results identify a novel IGF-II signaling axis and downstream targets that are regulated in a SOX9-dependent and -independent manner. Our findings provide novel insights on the role of IGF-II in promoting pulmonary fibrosis.

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Section: Sox9 In Pulmonary Fibrosissupporting

confidence: 78%

The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis

Waldrep

Rodgers

Garrett

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The modeling process was improved based on previous research. 13 All rats were purchased from Chongqing Medical University, and all animal use programs were approved by the Animal Care and Use Committee of the First Affiliated Hospital of Chongqing Medical University (No. 2022-112).…”

Section: Methodsmentioning

confidence: 99%

“… 12 A recent study from our lab has shown that SOX9 is up-regulated in the formation of tracheal granulation tissues in rat models, and SOX9 knockdown can alleviate tracheal fibrosis following brushing by preventing fibroblast inactivation and ECM deposition. 13 Therefore, we believe that SOX9 is involved in recurrent granulation tissue proliferation after tracheal injury, and the inhibition of SOX9 may be the key to solving this problem. However, the mechanism through which SOX9 regulates tracheal fibrosis remains unclear.…”

Section: Introductionmentioning

confidence: 99%