The injury-induced transcription factor SOX9 alters the expression of LBR, HMGA2, and HIPK3 in the human kidney
(2023) In American Journal of Physiology - Renal Physiology 324(1). p.75-90- Abstract
Induction of SRY box transcription factor 9 (SOX9) has been shown to occur in response to kidney injury in rodents, where SOX9-positive cells proliferate and regenerate the proximal tubules of injured kidneys. Additionally, SOX9-positive cells demonstrate a capacity to differentiate toward other nephron segments. Here, we characterized the role of SOX9 in normal and injured human kidneys. SOX9 expression was found to colocalize with a proportion of so-called scattered tubular cells in the uninjured kidney, a cell population previously shown to be involved in kidney injury and regeneration. Following injury and in areas adjacent to inflammatory cell infiltrates, SOX9-positive cells were increased in number. With the use of primary... (More)
Induction of SRY box transcription factor 9 (SOX9) has been shown to occur in response to kidney injury in rodents, where SOX9-positive cells proliferate and regenerate the proximal tubules of injured kidneys. Additionally, SOX9-positive cells demonstrate a capacity to differentiate toward other nephron segments. Here, we characterized the role of SOX9 in normal and injured human kidneys. SOX9 expression was found to colocalize with a proportion of so-called scattered tubular cells in the uninjured kidney, a cell population previously shown to be involved in kidney injury and regeneration. Following injury and in areas adjacent to inflammatory cell infiltrates, SOX9-positive cells were increased in number. With the use of primary tubular epithelial cells (PTECs) obtained from human kidney tissue, SOX9 expression was spontaneously induced in culture and further increased by transforming growth factor-b1, whereas it was suppressed by interferon-c. siRNA-mediated knockdown of SOX9 in PTECs followed by analysis of differential gene expression, immunohistochemical expression, and luciferase promoter assays suggested lamin B receptor (LBR), high mobility group AT-hook 2 (HMGA2), and homeodomain interacting protein kinase 3 (HIPK3) as possible target genes of SOX9. Moreover, a kidney explant model was used to demonstrate that only SOX9-positive cells survive the massive injury associated with kidney ischemia and that the surviving SOX9-positive cells spread and repopulate the tubules. Using a wound healing assay, we also showed that SOX9 positively regulated the migratory capacity of PTECs. These findings shed light on the functional and regulatory aspects of SOX9 activation in the human kidney during injury and regeneration.
(Less)
- author
- Kha, Michelle
; Krawczyk, Krzysztof
LU
; Choong, Oi Kuan ; De Luca, Francesco ; Altiparmak, Gulay ; Kallberg, Eva LU ; Nilsson, Helen LU ; Leandersson, Karin LU
; Sward, Karl LU and Johansson, Martin E.
- organization
- publishing date
- 2023-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- kidney injury, regeneration, SRY box transcription factor 9
- in
- American Journal of Physiology - Renal Physiology
- volume
- 324
- issue
- 1
- pages
- 75 - 90
- publisher
- American Physiological Society
- external identifiers
-
- pmid:36454702
- scopus:85144588898
- ISSN
- 1931-857X
- DOI
- 10.1152/ajprenal.00196.2022
- language
- English
- LU publication?
- yes
- id
- b295265c-5d16-4cf6-afcc-104b1a1aeb8a
- date added to LUP
- 2023-02-07 15:18:26
- date last changed
- 2024-06-28 01:10:26
@article{b295265c-5d16-4cf6-afcc-104b1a1aeb8a, abstract = {{<p>Induction of SRY box transcription factor 9 (SOX9) has been shown to occur in response to kidney injury in rodents, where SOX9-positive cells proliferate and regenerate the proximal tubules of injured kidneys. Additionally, SOX9-positive cells demonstrate a capacity to differentiate toward other nephron segments. Here, we characterized the role of SOX9 in normal and injured human kidneys. SOX9 expression was found to colocalize with a proportion of so-called scattered tubular cells in the uninjured kidney, a cell population previously shown to be involved in kidney injury and regeneration. Following injury and in areas adjacent to inflammatory cell infiltrates, SOX9-positive cells were increased in number. With the use of primary tubular epithelial cells (PTECs) obtained from human kidney tissue, SOX9 expression was spontaneously induced in culture and further increased by transforming growth factor-b1, whereas it was suppressed by interferon-c. siRNA-mediated knockdown of SOX9 in PTECs followed by analysis of differential gene expression, immunohistochemical expression, and luciferase promoter assays suggested lamin B receptor (LBR), high mobility group AT-hook 2 (HMGA2), and homeodomain interacting protein kinase 3 (HIPK3) as possible target genes of SOX9. Moreover, a kidney explant model was used to demonstrate that only SOX9-positive cells survive the massive injury associated with kidney ischemia and that the surviving SOX9-positive cells spread and repopulate the tubules. Using a wound healing assay, we also showed that SOX9 positively regulated the migratory capacity of PTECs. These findings shed light on the functional and regulatory aspects of SOX9 activation in the human kidney during injury and regeneration.</p>}}, author = {{Kha, Michelle and Krawczyk, Krzysztof and Choong, Oi Kuan and De Luca, Francesco and Altiparmak, Gulay and Kallberg, Eva and Nilsson, Helen and Leandersson, Karin and Sward, Karl and Johansson, Martin E.}}, issn = {{1931-857X}}, keywords = {{kidney injury; regeneration; SRY box transcription factor 9}}, language = {{eng}}, number = {{1}}, pages = {{75--90}}, publisher = {{American Physiological Society}}, series = {{American Journal of Physiology - Renal Physiology}}, title = {{The injury-induced transcription factor SOX9 alters the expression of LBR, HMGA2, and HIPK3 in the human kidney}}, url = {{http://dx.doi.org/10.1152/ajprenal.00196.2022}}, doi = {{10.1152/ajprenal.00196.2022}}, volume = {{324}}, year = {{2023}}, }