{
  "abstract": "ObjectiveTo investigate the regulatory role of the growth arrest-specific protein 6 （Gas6）/Axl receptor tyrosine kinase （Axl） signaling pathway in macrophage polarization， and to further elucidate its role and underlying mechanisms during the progression of interstitial fibrosis in immunoglobulin A nephropathy （IgAN）.MethodsM0-type macrophages were transfected with Axl-targeting small interfering RNA （siRNA） and negative control （NC） siRNA， respectively. Quantitative real-time polymerase chain reaction （qPCR） and Western blotting were used to detect the expression of Axl and M2-type macrophage-specific factors including cluster of differentiation 206 （CD206）， arginase-1 （Arg-1）， transforming growth factor-β （TGF-β）， and interleukin-10 （IL-10）. Flow cytometry was used to detect the proportions of M1- and M2-type macrophages. A co-culture system of human kidney-2 （HK-2） cells and M0-type macrophages was established and divided into a control group， a TGF-β1 group， a TGF-β1＋siRNA-NC group， and a TGF-β1＋siRNA-Axl group. Enzyme-linked immunosorbent assay （ELISA） was used to measure collagen （COL）1 and COL3 levels in culture supernatants. Immunofluorescence staining was used to observe α-smooth muscle actin （α-SMA） expression in HK-2 cells. Western blotting was used to detect α-SMA， fibronectin （FN）， Gas6， phosphorylated protein kinase B （p-Akt）， and protein kinase B （Akt） protein expression， and the p-Akt/Akt ratio was calculated. For the animal experiment， 10 wild type （WT） mice and 10 Axl gene knockout （Axl-/-） mice were randomly assigned （5 mice per group） into four groups： WT control group， WT IgAN group， Axl-/- control group， and Axl-/- IgAN group. Hematoxylin and eosin （HE） and Masson staining were used to assess renal pathological injury and fibrosis. Western blotting was used to detect α-SMA and FN protein expression. Immunofluorescence double staining was used to evaluate M2-type macrophage infiltration.ResultsIn vitro experiments showed that compared with the control group and siRNA-NC group， the siRNA-Axl group had lower relative Axl mRNA expression （0.28±0.02 vs 1.00±0.06， 1.02±0.08） and lower relative Axl protein expression （0.07±0.01 vs 0.35±0.03， 0.32±0.04）. The proportion of M1-type macrophages increased （［73.50±7.65］% vs ［50.00±6.02］%， ［51.00±4.98］%）， while the proportion of M2-type macrophages decreased （［25.50±2.71］% vs ［49.70±5.13］%， ［49.10±5.01］%）. The mRNA and protein expression of CD206， Arg-1， TGF-β， and IL-10 decreased （all P<0.05）. After co-culture of HK-2 cells with macrophages， compared with the control group， the TGF-β1 group showed increased COL1 （［2.07±0.21］ μg/L vs ［0.54±0.04］ μg/L） and COL3 （［1.53±0.14］ μg/L vs ［0.42±0.04］ μg/L）， enhanced α-SMA immunofluorescence expression， and increased relative expression of α-SMA （0.72±0.06 vs 0.11±0.01）， FN （0.70±0.08 vs 0.09±0.01）， and Gas6 （0.68±0.07 vs 0.06±0.01）， as well as an increased p-Akt/Akt ratio （0.34±0.03 vs 0.12±0.01）. Compared with the TGF-β1＋siRNA-NC group， the TGF-β1＋siRNA-Axl group showed decreased COL1 （［1.01±0.08］ μg/L vs ［2.06±0.21］ μg/L） and COL3 （［0.73±0.06］ μg/L vs ［1.53±0.14］ μg/L）， weakened α-SMA immunofluorescence expression， and decreased relative protein expression of α-SMA （0.15±0.02 vs 0.74±0.08）， FN （0.17±0.02 vs 0.73±0.08）， and Gas6 （0.15±0.01 vs 0.66±0.07）， as well as a decreased p-Akt/Akt ratio （0.21±0.02 vs 0.32±0.03） （all P<0.05）. In animal experiments， compared with the WT control group， the WT IgAN group showed increased renal interstitial fibrosis area （［12.46±1.34］% vs ［1.23±0.14］%）， increased relative protein expression of α-SMA （1.27±0.13 vs 0.43±0.04） and FN （0.93±0.10 vs 0.14±0.01）， and increased M2-type macrophage proportion （［21.50±2.24］% vs ［6.34±0.65］%）. Compared with the Axl-/- control group， the Axl-/- IgAN group showed increased renal interstitial fibrosis area （［7.54±0.80］% vs ［1.01±0.11］%）， increased relative protein expression of α-SMA （0.63±0.06 vs 0.42±0.04） and FN （0.47±0.05 vs 0.13±0.01）， and increased M2-type macrophage proportion （［17.83±1.84］% vs ［6.81±0.67］%）. Compared with the WT IgAN group， the Axl-/- IgAN group showed decreased renal interstitial fibrosis area （［7.54±0.80］% vs ［12.46±1.34］%）， decreased relative protein expression of α-SMA （0.63±0.06 vs 1.27±0.13） and FN （0.47±0.05 vs 0.93±0.10）， and decreased M2-type macrophage proportion （［17.83±1.84］% vs ［21.50±2.24］%） （P<0.05）.ConclusionThe Gas6/Axl signaling pathway participates in the progression of interstitial fibrosis in IgAN by regulating macrophage polarization. Axl silencing or knockout can alleviate renal interstitial fibrosis injury， providing a potential target for IgAN treatment.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
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  "author_total": 7,
  "authors": [
    {
      "name": "Yang Shu-fen"
    },
    {
      "name": "Zhu Guo-qiang"
    },
    {
      "name": "Meng Zhao-xi"
    },
    {
      "name": "Jiang Hong"
    },
    {
      "name": "Yalikun Dilina"
    },
    {
      "name": "Bai Lu"
    },
    {
      "name": "Ha Xiao-wen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dffrcrpx3hrtd.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": "http://www.lcszb.com/thesisDetails#10.3969/j.issn.1671-2390.2026.10.009",
  "id": "dffrcrpx3hrtd",
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  "language": "zh",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
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  "native_subjects": [
    [
      "lcc",
      "RC31-1245"
    ]
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  "openalex": null,
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  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "Editorial Department of Journal of Clinical Nephrology",
  "ris": "https://research.draconitic.com/paper/dffrcrpx3hrtd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:45Z",
      "native_id": "7b547f5d075846cc80eac81c66ceaa3e",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC31-1245",
      "subfield": "general"
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  ],
  "title": "Mechanism of growth arrest-specific protein 6/Axl receptor tyrosine kinase signaling pathway in promoting macrophage polarization and contributing to interstitial fibrosis in IgA nephropathy",
  "title_text": "Mechanism of growth arrest-specific protein 6/Axl receptor tyrosine kinase signaling pathway in promoting macrophage polarization and contributing to interstitial fibrosis in IgA nephropathy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:45Z",
  "url": "https://research.draconitic.com/paper/dffrcrpx3hrtd",
  "venue": "Linchuang shenzangbing zazhi",
  "versions": []
}