Exploring Integrins in Smooth Muscle Function: Addressing Challenging Levels of Complexity and Deciphering Organ-specific Codes of Contraction?

Hennenberg, Martin

doi:10.1093/function/zqac053

Cited by 1 publication

(1 citation statement)

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“…WNK1 was identified as the most strongly activated kinase involved in corneal wound healing, depending on concerted interactions of cell migration, adhesion, proliferation, differentiation, and extracellular matrix production 64 . Inhibition of corneal wound healing by WNK463 involved intregrins, including α5 which has been related to smooth muscle contraction, 65 and further adhesion molecules. Microarray analyses after treatment of corneal epithelial cells with 1 μM WNK463 suggested WNK‐driven migration, proliferation and differentiation 66 .…”

Section: Discussionmentioning

confidence: 99%

Isoform‐independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells

Liu,

Huang,

Wang

et al. 2024

The FASEB Journal

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With no lysine/K kinases (WNKs) promote vasocontraction and vascular smooth muscle cell proliferation. In the prostate, smooth muscle contraction and growth may be critical for the development and medical treatment of voiding symptoms in benign prostatic hyperplasia. Here, we examined the effects of isoform‐specific WNK silencing and of the WNK inhibitor WNK463 on growth‐related functions and contraction in prostate stromal cells, and in human prostate tissues. Impacts of WNK silencing by transfection of cultured stromal cells with isoform‐specific siRNAs were qualitatively and quantitatively similar for each WNK isoform. Effects of silencing were largest on cell death (3–5 fold increase in annexin V‐positive/7‐AAD‐positive cells), on proliferation rate, Ki‐67 mRNA expression and actin organization (reduced around two‐thirds). Contraction in matrix contraction assays and viability were reduced to a lower degree (approximately half), but again to a similar extent for each WNK isoform. Effects of silencing were quantitatively and qualitatively reproduced by 10 μM WNK463, while 1 μM still induced cell death and breakdown in actin organization, without affecting proliferation or viability. Using 500 nM and 10 μM, WNK463 partly inhibited neurogenic and U46619‐induced contractions of human prostate tissues (around half), while inhibition of α1‐adrenergic contractions (around half) was limited to 10 μM. All four WNK isoforms suppress cell death and promote proliferation in prostate stromal cells. WNK‐driven contraction of stromal cells appears possible, even though to a limited extent. Outcomes of isoform‐specific WNK silencing can be fully reproduced by WNK463, including inhibition of smooth muscle contraction in human prostate tissues, but require high concentrations.

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Section: Discussionmentioning

confidence: 99%